Knut Lundin

• Hjort, Rebecka; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Jonkers, Iris & Lundin, Knut [Vis alle 10 forfattere av denne artikkelen] (2026). Human Leukocyte Antigen-DQ Allotypes in Adults Screened for Celiac Disease Reveal Historical Misdiagnosis - Results From the Trøndelag Health Study. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. doi: 10.1016/j.cgh.2026.07.033. Fulltekst i vitenarkiv
• Rapp, Emma; Berset, Ingrid Prytz; Umu, Sinan Ugur; Bækkevold, Espen Sønderaal; Utheim, Karen Sivertsen & Dietrich, Alexander [Vis alle 13 forfattere av denne artikkelen] (2026). Longitudinal transcriptomic analysis of mucosa in ulcerative colitis after anti-tumor necrosis factor withdrawal compared to continued treatment. Journal of Crohn's and Colitis. ISSN 1873-9946. 20(8). doi: 10.1093/ecco-jcc/jjag121. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims Monoclonal antibodies against tumor necrosis factor (anti-TNF) are effective agents in the treatment of moderate-to-severe ulcerative colitis (UC). It is unclear whether such treatment can safely be discontinued without relapse. This study aimed to identify biomarkers to predict which patients can successfully stop anti-TNF treatment, and to increase our understanding of the pathogenesis of relapse after withdrawal and flare on continued therapy. Methods We analyzed longitudinal bulk RNA-sequencing data derived from rectal mucosal biopsies from 163 patients in the BIOSTOP study collected at baseline, after 2 years (end of study), and at flares or relapse points. Results In this cohort, pre-withdrawal transcriptomic profiles did not distinguish patients who later relapsed from those who remained in long-term remission. Longitudinal analysis of patients who relapsed or flared were both characterized by inflammatory gene expression profiles (eg, CXCL9, CXCL10, OSMR, SELE) and changes in cell-type composition typical for active UC (eg, monocytes/macrophages and THY1+ FAP+ PDPN+ activated fibroblasts). Both groups showed enrichment of T-cell-associated transcriptional signatures, including CD8 T-cell-related genes and IL-17-associated pathways. Additionally, both patient groups showed increased expression of targets of alternative therapeutic agents, suggesting potential treatment options for specific patient subgroups. Conclusions Our findings provide insights into the inflammatory mechanisms driving relapse after anti-TNF withdrawal and flare on continued treatment. The dataset offers a valuable resource for future research to improve personalized treatment strategies in UC.

• Myhre, Vegard; Kaarbø, Mari; Yang, Mingyi; Fevang, Børre; Sousa, Mirta Mittelstedt Leal de & Reims, Henrik Mikael [Vis alle 11 forfattere av denne artikkelen] (2026). Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1875823. Fulltekst i vitenarkiv
• Lindeman, Ida; Officer, Aengus; Dahal-Koirala, Shiva; Risnes, Louise Fremgaard; Hjort, Rebecka & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2026). A predisposing effect of HLA class II genes in celiac disease by skewing the naive CD4⁺T cell receptor repertoire. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 123(26). doi: 10.1073/pnas.2520636123. Fulltekst i vitenarkiv
• Berset, Ingrid Prytz; Lerang, Frode; Moum, Bjørn Allan; Jahnsen, Jørgen; Grimstad, Tore Bjørn & Kristensen, Vendel Ailin [Vis alle 26 forfattere av denne artikkelen] (2026). Anti-TNF withdrawal or long-term treatment in ulcerative colitis (BIOSTOP): a multicentre open label, randomized controlled trial. Journal of Crohn's and Colitis. ISSN 1873-9946. 20(8). doi: 10.1093/ecco-jcc/jjag110. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims: Anti-tumour necrosis factor (anti-TNF) treatment is effective in ulcerative colitis (UC). Optimal treatment duration is uncertain. This trial studies outcome after anti-TNF withdrawal compared to maintenance treatment in UC. Methods: In this prospective, multicentre, randomized, controlled, open-label non-inferiority study, patients in deep clinical, biochemical and endoscopic remission were randomized 1:1 to anti-TNF withdrawal or maintenance treatment. Primary endpoint was endoscopically confirmed remission (Mayo Endoscopic Score 0 or 1) after two years, including UC flares treated with anti-TNF, or non-biologic agents. Secondary endpoints were clinical remission, UC flare rate and treatment response. We needed 170 participants to show non-inferiority with a 15% margin. Results: Between June 2017 and December 2021, 172 UC patients from 19 Norwegian hospitals were randomized; 86 in each group. The per-protocol population was 163 patients. Nine patients were excluded due to consent withdrawal or protocol violation. Eighty percent (66/82) of anti-TNF withdrawal and 96% (78/81) of maintenance patients were in endoscopic remission after 2 years. UC flares occurred in 52% (45/86) of withdrawal and 12% (10/86) of maintenance patients. Anti-TNF retreatment was successful in 74% (20/27). Conclusion: Two years after anti-TNF withdrawal in UC patients in deep remission, endoscopically confirmed remission rate was significantly lower compared to maintenance treatment. Non-inferiority could not be proven. UC flare rate after anti-TNF withdrawal was high, but most were successfully treated. The majority did not receive AZA. Importantly, 48% of anti-TNF withdrawal patients remained in steroid-free remission. No significant predictors for UC activity after anti-TNF withdrawal were identified.

• Vaz, Filipa Baltazar da Costa; Lindeman, Ida; Hoffmann, Henriette H.; Skagen, Christine; Steffensen, Anne Katrine & Bjørnholt, Jørgen Vildershøj [Vis alle 10 forfattere av denne artikkelen] (2026). Distinct systemic and gut IgA responses to bacteria of the human upper gastrointestinal tract. Cell reports. 45(8), s. 1–21. doi: 10.1016/j.celrep.2026.117721. Fulltekst i vitenarkiv
• Alam, Mohammad Sayeef; Hjort, Rebecka; Jonkers, Iris H.; Withoff, Sebo; Hveem, Kristian & Lundin, Knut [Vis alle 8 forfattere av denne artikkelen] (2026). A model for predicting celiac disease among undiagnosed subjects established with data from the HUNT4 study. BMC Gastroenterology. 26(1). doi: 10.1186/s12876-026-04837-y. Fulltekst i vitenarkiv
• Ibsen, Jostein Holen; Rud, Ane Kristine Kongsgaard; Sovershaev, Michael; Lund, Stine Rosenqvist; Paulsen, Vemund & Darre-Næss, Ole [Vis alle 11 forfattere av denne artikkelen] (2026). Serology-based diagnosis of coeliac disease in secondary care: a single-centre study in Norway. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 61(3), s. 257–267. doi: 10.1080/00365521.2026.2615407. Fulltekst i vitenarkiv
• Officer, Aengus; Watson, Corey T.; Engelbrecht, Eric; Dahal-Koirala, Shiva; Risnes, Louise Fremgaard & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2026). Immunoglobulin gene polymorphisms shape the naïve B-cell receptor repertoire; relevance to celiac disease. Genes and Immunity. ISSN 1466-4879. 27, s. 210–222. doi: 10.1038/s41435-026-00384-4. Fulltekst i vitenarkiv
• Ciacci, Carolina; Adams, Dawn W.; Lundin, Knut & Niveloni, Sonia (2025). Current Recommendations for Diagnosis of Celiac Disease. Gastrointestinal Endoscopy Clinics of North America. ISSN 1052-5157. 35(4), s. 725–738. doi: 10.1016/j.giec.2025.01.005. Fulltekst i vitenarkiv
• Risnes, Louise Fremgaard; Brottveit, Margit; Robertsen, Ida; Ibsen, Jostein Holen; Aabakken, Lars & Johannesen, Marie Kongshaug [Vis alle 12 forfattere av denne artikkelen] (2025). Research Communication: Teriflunomide Does Not Affect Gluten-Specific T-Cell Activity in Coeliac Disease—A Randomised, Placebo-Controlled Trial. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 62(10), s. 1027–1031. doi: 10.1111/apt.70301. Fulltekst i vitenarkiv Vis sammendrag

  Coeliac disease is an autoimmune disorder driven by gluten and managed through a strict gluten-free diet. We tested teriflunomide, a drug known for its ability to alter T-cell activity, in a phase 2a trial of 15 patients with coeliac disease. Participants received teriflunomide or placebo including a loading dose, followed by a 3-day oral gluten challenge to monitor T-cell responses. The main aim was to observe attenuation of gluten-specific T-cell activation markers after gluten exposure. We found no significant differences in T-cell activity between groups, concluding that teriflunomide is ineffective as a non-dietary treatment for coeliac disease

• Al-Toma, Abdulbaqi; Zingone, Fabiana; Branchi, Federica; Schiepatti, Annalisa; Malamut, Georgia & Canova, Cristina [Vis alle 21 forfattere av denne artikkelen] (2025). European Society for the Study of Coeliac Disease 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 1: Diagnostic Approach. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 13(10), s. 1855–1886. doi: 10.1002/ueg2.70119. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Since the publication of the first European Society for the Study of Coeliac Disease (ESsCD) guidelines in 2019, significant advancements have emerged in the diagnosis of coeliac disease (CeD) in adults. These 2025 guidelines incorporate new evidence to refine diagnostic strategies, aiming for improved accuracy of testing, and enhance overall quality of clinical care. Methods A multidisciplinary panel of experts revised the ESsCD guidelines using the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation II) and the GRADE methodology (The Grading of Recommendations Assessment, Development, and Evaluation). Clinical questions were structured using the PICO format, and statements and recommendations were finalised through a Delphi consensus process. Literature quality was assessed using AMSTAR-2 and QUADAS-2 tools. Results The updated guidelines are presented in two parts. Part 1 focuses on adult CeD diagnosis, introducing major changes such as a conditional no-biopsy approach for selected adults with high-titre IgA anti-TG2 serology (≥ 10 × ULN). Regarding serology, the use of validated high-performance ELISAs displaying a high diagnostic accuracy is emphasised, while routine use of IgA anti-Endomysium serology is no longer recommended for confirmation. Revised duodenal biopsy protocols now mandate at least four samples from the second part of the duodenum, with bulb biopsies conditionally included. The guidelines provide structured approaches for diagnosing potential CeD, seronegative villous atrophy, and CeD in individuals already on a gluten-free diet. HLA-DQ2/DQ8 typing is recommended for diagnostic clarification in select cases. Conclusions The updated 2025 ESsCD guidelines provide a comprehensive framework for the diagnosis of CeD in adults. By integrating evolving diagnostic strategies, minimising over-testing, and patient-centred care approaches, they aim to optimise patient outcomes, quality of life and use of diagnostic resources at the same time.

• Stamnæs, Jorunn; Stray, Daniel; Pré, Marie Fleur du; Risnes, Louise Fremgaard; Dewan, Alisa & Shaik, Jakeer [Vis alle 9 forfattere av denne artikkelen] (2025). IFN-gamma is a direct driver of crypt hyperplasia in celiac disease. Journal of Clinical Investigation. ISSN 0021-9738. 135(20). doi: 10.1172/JCI194858. Fulltekst i vitenarkiv Vis sammendrag

  Crypt hyperplasia is a key feature of celiac disease (CeD) and several other small intestinal inflammatory conditions. Analysis of the gut epithelial crypt zone by mass spectrometry–based tissue proteomics revealed a strong IFN-γ signal in active CeD. This signal, hallmarked by increased expression of MHC molecules, was paralleled by diminished expression of proteins associated with fatty acid metabolism. Crypt hyperplasia and the same proteomic changes were observed in WT mice administered IFN-γ. In mice with conditional KO of the IFN-γ receptor in gut epithelial cells, these signature morphological and proteomic changes were not induced with IFN-γ administration. IFN-γ was thus a driver of crypt hyperplasia in CeD by acting directly on crypt epithelial cells. The results are relevant to other enteropathies with involvement of IFN-γ.

• Carlsen, Arne; Steinsbø, Øyvind; Kvaløy, Jan Terje; Aabakken, Lars; Bolstad, Nils & Warren, David John [Vis alle 10 forfattere av denne artikkelen] (2025). Optimizing serum adalimumab levels in maintenance therapy via proactive therapeutic drug monitoring improves markers of disease activity in Crohn’s disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 60(12), s. 1214–1225. doi: 10.1080/00365521.2025.2573725. Fulltekst i vitenarkiv Vis sammendrag

  Objects The benefit of a proactive therapeutic drug monitoring (TDM) strategy in patients with inflammatory bowel disease receiving biological therapy remains disputed. We aimed to evaluate whether optimizing serum adalimumab levels (s-ADL), guided by proactive TDM, is associated with improved markers of disease activity in patients with Crohn’s disease. Materials and methods In this longitudinal cross-sectional study, 72 patients receiving adalimumab maintenance therapy from our outpatient clinic, were included. Patients underwent five study visits at 3-month intervals over one year. Disease activity was assesed using the Harvey-Bradshaw Index, plasma C-reactive protein (CRP), and fecal calprotectin. s-ADL levels were measured at each visit, and dosing was adjusted to maintain a therapeutic target range of 5.0–12.0 mg/L. Results At baseline, subtherapeutic s-ADL levels were associated with higher CRP levels (p = 0.03), and in these patients’ drug levels increased significantly over the study (p = 0.001), whereas CRP levels decreased (p = 0.03). Longitudinal analysis demonstrated that higher s-ADL levels (≥5.0 mg/L) were associated with lower CRP levels (p = 0.008) and lower HBI scores (p = 0.03). Additionally, lower CRP- and fecal calprotectin levels at any visit were associated with higher s-ADL levels at the preceding visit (p = 0.04 for both). Lower CRP levels were also associated with higher s-ADL levels using 7.0 mg/L as the therapeutic threshold in longitudinal analyses (p = 0.003). Conclusion Proactive TDM-guided optimization of s-ADL levels in Crohn’s disease patients on adalimumab maintenance therapy was associated with the modest but significant improvements in markers of disease activity over one year of follow-up.

• Melby, Kjetil K.; Hjort, Rebecka; Lundin, Knut & Ness-Jensen, Eivind (2025). Infection with Helicobacter pylori and the age at onset of coeliac disease in the “HUNT4” survey. BMC Research Notes. 19. doi: 10.1186/s13104-025-07594-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objective This study aimed to determine whether H. pylori or its antigens affect the age at which coeliac disease (CeD) was diagnosed. Participants over 20 years old from the HUNT4 survey were screened for CeD by measuring serum immunoglobulin A and immunoglobulin G antibodies against transglutaminase-2. H. pylori status was defined by detecting H. pylori -specific immunoglobulin G. Results H. pylori  + participants had a mean age of 62.3 years, compared to 54.8 years for negative participants. In those with previously undiagnosed CeD ( n  = 43), higher antibody levels against GroEL were associated with an older age at sampling (67.2 years for GroEL-positive vs. 50.8 years for negative). Smaller age differences were noted for gGT (6.0 years), UreA (8.6 years), and HpcC (6.4 years), while vacA and cagA showed only minor differences. Participants with CeD and H. pylori  + were older than those who were H. pylori −. The presence of antigens such as GroEL, gGT, and UreA appeared to be associated with this age difference. Aside from H. pylori infection in childhood, a cohort effect of H. pylori infection may partly explain the differences.

• D., Ramírez-Sánchez, Aarón; Zühlke, Stephanie; Raúl, Aguirre-Gamboa,; Martijn, Vochteloo,; Lude, Franke, & Lundin, Knut [Vis alle 8 forfattere av denne artikkelen] (2025). Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease | Genes & Immunity. Genes and Immunity. ISSN 1466-4879. 26, s. 519–530. doi: 10.1038/s41435-025-00356-0. Fulltekst i vitenarkiv Vis sammendrag

  In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD. We identified 1 862 differential expressed genes, which clustered into four sets. Two sets, one upregulated for cell cycle function (n = 366) and one downregulated for digestion, transmembrane transport, and laminin pathways (n = 543), defined three sample groups based on inflammation status: non-inflamed, mild inflammation or severe inflammation. The remaining two sets of genes were enriched for immune (n = 458) and extracellular matrix and barrier functions (n = 495) and were sufficient to classify samples into their disease conditions. Finally, deconvoluting eQTL effects from epithelial and immune cells identified 6 and 15 cell-type-mediated eQTL genes, respectively. In sum, we identified genes expressed in the duodenal EL whose expression reflect heterogeneity in CeD and that may be used as biomarkers to assess CeD condition and its mucosal and immune status.

• Alam, Mohammad Sayeef; Wolford, Brooke N.; Hveem, Kristian; Lundin, Knut; Withoff, Sebo & Jonkers, Iris H. [Vis alle 9 forfattere av denne artikkelen] (2025). Genetic differences between diagnosed and undiagnosed Celiac disease: a population-based study. Human Genetics. ISSN 0340-6717. 144, s. 1071–1078. doi: 10.1007/s00439-025-02778-2. Fulltekst i vitenarkiv Vis sammendrag

  A large proportion of individuals with celiac disease (CeD) remain undiagnosed, often presenting at an older age of onset or with non-classical symptoms compared to diagnosed cases. Such heterogeneity might be related to genetic factors. The aim was to utilize a CeD-screened adult population to compare the genetic variants in known and newly diagnosed cases. In the fourth wave of the population-based Trøndelag Health Study (HUNT4) 826 CeD and 51,516 non-CeD individuals were included. Medical registries identified 361 previously diagnosed cases, while screening identified 465 new cases. A validated polygenic risk score (PRS) was used to assess the genetic risk of CeD among the two case groups versus non-CeD individuals. Additional genetic variants not included in the PRS were also analyzed. The PRS distinguished cases from non-cases with high accuracy (AUROC: 85% for known cases, 83% for new cases). The genetic variation explained by the PRS was similar for known and new cases (17.1% versus 14.5%). The odds ratio for being in the highest genetic risk group (top 10%) was 22.7 (95% CI 14.1–36.4) for known cases and 18.6 (95% CI 12.4–27.9) for new cases versus the median group (40%-60%). Differences in effect size among specific genome-wide variants were observed but were not significantly associated with CeD. A validated PRS showed significant genetic difference between CeD cases and the general population, with similar association in both known and newly diagnosed cases. This suggests that genetic architectures of the two groups are comparable, implying that other non-genetic factors may drive CeD in adults.

• Alam, Mohammad Sayeef; Thomas, Laurent Francois; Brumpton, Ben Michael; Hveem, Kristian; Lundin, Knut & Withoff, Sebo [Vis alle 10 forfattere av denne artikkelen] (2025). Population screening of adults identifies novel genetic variants associated with celiac disease. Scientific Reports. 15(1). doi: 10.1038/s41598-025-04421-6. Fulltekst i vitenarkiv Vis sammendrag

  Celiac disease (CeD) is an autoimmune disease driven by a complex genetic interplay within and beyond the human leukocyte antigen (HLA) region. Despite this, half of its heritability remains unexplained, with most of the unidentified variants located in non-protein coding regions. Here we performed a genome-wide association study among 52,342 adults screened for CeD, including 465 previously undiagnosed and 361 already diagnosed cases, which mitigated the likely disease misclassification present in previous studies. Genotyping and imputation yielded approximately 24.9 million variants for analysis. The study identified 15 novel associations (P < 5E-08) in 12 loci in addition to all the previously associated loci at lower significance thresholds (P < 5E-03). The 5p15.33 locus in the long non-coding RNA gene (LINC01019) showed the highest potential for a true association with CeD. Notably, variants in 5p15.33 has also been associated with rheumatoid arthritis, suggesting a new shared autoimmune locus.

• Grimstad, Tore Bjørn; Carlsen, Arne; Kvaløy, Jan Terje; Bolstad, Nils; Warren, David & Aabakken, Lars [Vis alle 10 forfattere av denne artikkelen] (2025). Fatigue in Inflammatory Bowel Disease: No Effect of Serum Concentrations of Infliximab, Adalimumab or Anti-Drug Antibodies During Maintenance Therapy. Scandinavian Journal of Immunology. ISSN 0300-9475. 101(5). doi: 10.1111/sji.70029. Fulltekst i vitenarkiv Vis sammendrag

  Several studies have shown that infliximab and adalimumab ameliorate fatigue in inflammatory bowel disease. We investigated whether serum levels of these agents above or below a selected threshold influence fatigue severity. In this cross-sectional study, we measured serum concentrations (s-) of infliximab and adalimumab and corresponding anti-drug antibody levels. Therapeutic thresholds were defined as s-infliximab ≥ 5.0 mg/L and s-adalimumab ≥ 7.0 mg/L. Disease activity was assessed using the Harvey–Bradshaw Index for Crohn's disease, Partial Mayo Score for ulcerative colitis, and C-reactive protein (CRP) and faecal calprotectin levels for both conditions. Fatigue was assessed with the Fatigue Visual Analog Scale and Fatigue Severity Scale, and depression was evaluated with the Hospital Anxiety and Depression Scale, Depression subscale. Of 171 included patients (112 with Crohn's disease, 59 with ulcerative colitis), 66 (38.6%) were on infliximab and 105 (61.4%) were on adalimumab. Scores on the two fatigue scales were similar for serum values above versus below therapeutic thresholds for both drugs and did not differ with versus without anti-drug antibodies against either drug. CRP was numerically higher with infliximab levels below versus above the threshold (p = 0.06), whereas both CRP and faecal calprotectin were increased with adalimumab below versus above the threshold (p = 0.022, p = 0.0242). In patients with inflammatory bowel disease on maintenance therapy, s-infliximab and s-adalimumab levels below or above therapeutic thresholds or the presence of anti-drug antibodies did not affect fatigue severity.

• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf; Warren, David John; Bolstad, Nils & Mjønes, Patricia Gjertrud [Vis alle 11 forfattere av denne artikkelen] (2025). The Prevalence and Rate of Undiagnosed Celiac Disease in an Adult General Population, the Trøndelag Health Study, Norway. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 23(7), s. 1143–1151. doi: 10.1016/j.cgh.2024.06.027. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims This study aimed to determine the total prevalence of celiac disease (CeD), including undiagnosed cases, in a population-based study of adults screened for CeD. Methods The study used the fourth Trøndelag Health Study (HUNT4), conducted in 2017–2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analyzed for anti-transglutaminase 2 IgA and IgG. Seropositive individuals were invited for a clinical assessment, including upper endoscopy with duodenal biopsies. Previously diagnosed and seronegative CeD cases were identified through linkage to hospital records and the Norwegian Patient Registry. Results The rate of CeD seropositivity was 2.0% (1107/54,505). Out of these, 724 individuals attended the clinical assessment. Additionally, the hospital records and registry identified individuals with a known CeD diagnosis, that were seronegative or without serology in HUNT4 or seropositive in HUNT4 but did not participate in the clinical assessment. In total, the study confirmed a new CeD diagnosis after participation in HUNT4 in 470 individuals and a known CeD diagnosis before participation in HUNT4 in 383 individuals. The total biopsy-confirmed prevalence of CeD was 1.5% (853/56,042), and the ratio of new, previously undiagnosed CeD cases (after HUNT4) to known, previously diagnosed CeD cases (before HUNT4) was 1.2:1 (470/383). Conclusions The total prevalence of CeD in this population-based study of adults in Norway was high and many individuals were previously undiagnosed. Detection of CeD should be improved, because early diagnosis is crucial for effective management and prevention of complications.

• Andersen, Ina Lervåg; Lukina, Polina; Dyrli, Ole Thomas; Klaasen, Rolf; Warren, David & Bolstad, Nils [Vis alle 12 forfattere av denne artikkelen] (2025). Serological screening for coeliac disease in an adult general population: the HUNT study. Gut. ISSN 0017-5749. 74(6), s. 918–925. doi: 10.1136/gutjnl-2024-333886. Fulltekst i vitenarkiv Vis sammendrag

  Background A large proportion of individuals with coeliac disease (CeD) remain undiagnosed. Objective The aim of this study was to assess serological screening for CeD in the adult general population. Design The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found. Results Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals. Conclusion The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.

• Schiepatti, Annalisa; Maimaris, Stiliano; Scalvini, Davide; Raju, Suneil; Ingham, Katerina E & Johnson, Calvin M [Vis alle 23 forfattere av denne artikkelen] (2025). LONG-TERM PROGNOSIS of NON-CELIAC ENTEROPATHIES and A SCORE to IDENTIFY PATIENTS with POOR OUTCOMES: A 30-YEAR MULTICENTER LONGITUDINAL STUDY. American Journal of Gastroenterology. ISSN 0002-9270. doi: 10.14309/ajg.0000000000003331. Fulltekst i vitenarkiv
• Fretheim, Håvard Halland; Barua, Imon Shoumitra; Bakland, Gunnstein; Dhainaut, Alvilde Sofie Strand; Halse, Anne Kristine Hjorteseth & Nordgård, Maylen Carstens [Vis alle 21 forfattere av denne artikkelen] (2025). Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial. The Lancet Rheumatology. 7(5), s. e323–e332. doi: 10.1016/S2665-9913(24)00334-5. Fulltekst i vitenarkiv Vis sammendrag

  Background: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement. Methods: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426. Findings: Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58·91 years (SD 11·59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0·13, 95% CI -0·37 to 0·11) and participants who received placebo (-0·33, -0·57 to -0·09; average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation. Interpretation: Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms. Funding: KLINBEFORSK. Translation: For the Norwegian translation of the abstract see Supplementary Materials section.

• Risnes, Louise Fremgaard; Reims, Henrik Mikael; Doyle, Ronan Mathieu; Qiao, Shuo-Wang; Sollid, Ludvig Magne & Lundin, Knut [Vis alle 7 forfattere av denne artikkelen] (2024). Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease. Gastroenterology. ISSN 0016-5085. 167(2), s. 250–263. doi: 10.1053/j.gastro.2024.03.027. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment. Methods We followed 17 CeD patients during their initial GFD year, leading to disease remission. We assessed activation and frequency of gluten-specific CD4+ blood and gut T cells with HLA-DQ2.5:gluten tetramers and flow cytometry, disease-specific serology, histology, and symptom scores. We assessed gluten-specific blood T cells within the first 3 weeks of GFD in 6 patients and serology in an additional 9 patients. Results Gluten-specific CD4+ T cells peaked in blood at day 14 while up-regulating Bcl-2 and down-regulating Ki-67 and then decreased in frequency within 10 weeks of GFD. CD38, ICOS, HLA-DR, and Ki-67 decreased in gluten-specific cells within 3 days. PD-1, CD39, and OX40 expression persisted even after 12 months. IgA–transglutaminase 2 decreased significantly within 4 weeks. Conclusions GFD induces rapid changes in the phenotype and number of gluten-specific CD4+ blood T cells, including a peak of nonproliferating, nonapoptotic cells at day 14. Subsequent alterations in T-cell phenotype associate with the quiescent but chronic nature of treated CeD. The rapid changes affecting gluten-specific T cells and disease-specific antibodies offer opportunities for clinical trials aiming at developing nondietary treatments for patients with newly diagnosed CeD.

• Lukina, Polina; Andersen, Ina Lervåg; Eggen, Petter Tinbod; Mjønes, Patricia Gjertrud; Rønne, Elin & Bolstad, Nils [Vis alle 18 forfattere av denne artikkelen] (2024). Coeliac disease in the Trøndelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients. BMJ Open. 14:e077131(1), s. 1–7. doi: 10.1136/bmjopen-2023-077131. Fulltekst i vitenarkiv Vis sammendrag

  Purpose - Coeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease. Participants - The cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017–2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR). A total of 54 541 HUNT4 participants with available sera were screened for CD by serology. All seropositive participants were invited to a clinical assessment, including endoscopy with duodenal biopsies, during 2019–2023. Findings to date - A total of 1107 HUNT4 participants (2%) were seropositive for CD and 1048 were eligible for clinical assessment, including biopsy. Of these, 724 participants attended the clinical assessment and 482 were identified with CD. In addition, 371 participants with CD were identified through the hospital records and NPR. In total, 853 participants in HUNT4 with biopsy-verified CD diagnosis were identified. Future plans - All participants in the study will be invited to a follow-up assessment after at least 1 year, including repeated standard serological testing, endoscopy and tissue sampling. The collected data and material will be used to establish the true population-based prevalence of CD. The consequences of CD, including symptoms, deficiencies and comorbidity, will be investigated and possible triggers and predictors, will be studied. With access to serum samples from the previous HUNT surveys in HUNT Biobank, serological signs of CD in prediagnostic samples of seropositive individuals will be used. Genetic studies will identify new CD markers, assess genotype–phenotype links and explore gene–environment correlations.

• Johansen, Anette; Sandve, Geir Kjetil Ferkingstad; Ibsen, Jostein Holen; Lundin, Knut; Sollid, Ludvig Magne & Stamnæs, Jorunn (2024). Biopsy Proteome Scoring to Determine Mucosal Remodeling in Celiac Disease. Gastroenterology. ISSN 0016-5085. 167(3), s. 493–504. doi: 10.1053/j.gastro.2024.03.006. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims Histologic evaluation of gut biopsies is a cornerstone for diagnosis and management of celiac disease (CeD). Despite its wide use, the method depends on proper biopsy orientation, and it suffers from interobserver variability. Biopsy proteome measurement reporting on the tissue state can be obtained by mass spectrometry analysis of formalin-fixed paraffin-embedded tissue. Here we aimed to transform biopsy proteome data into numerical scores that give observer-independent measures of mucosal remodeling in CeD. Methods A pipeline using glass-mounted formalin-fixed paraffin-embedded sections for mass spectrometry-based proteome analysis was established. Proteome data were converted to numerical scores using 2 complementary approaches: a rank-based enrichment score and a score based on machine learning using logistic regression. The 2 scoring approaches were compared with each other and with histology analyzing 18 patients with CeD with biopsies collected before and after treatment with a gluten-free diet as well as biopsies from patients with CeD with varying degree of remission (n = 22). Biopsies from individuals without CeD (n = 32) were also analyzed. Results The method yielded reliable proteome scoring of both unstained and H&E-stained glass-mounted sections. The scores of the 2 approaches were highly correlated, reflecting that both approaches pick up proteome changes in the same biological pathways. The proteome scores correlated with villus height-to-crypt depth ratio. Thus, the method is able to score biopsies with poor orientation. Conclusions Biopsy proteome scores give reliable observer and orientation-independent measures of mucosal remodeling in CeD. The proteomic method can readily be implemented by nonexpert laboratories in parallel to histology assessment and easily scaled for clinical trial settings.

• Dotsenko, Valeriia; Tewes, Bernhard; Hils, Martin; Pasternack, Ralf; Isola, Jorma & Taavela, Juha [Vis alle 34 forfattere av denne artikkelen] (2024). Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease. Nature Immunology. ISSN 1529-2908. 25, s. 1218–1230. doi: 10.1038/s41590-024-01867-0. Fulltekst i vitenarkiv Vis sammendrag

  Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

• Lindeman, Ida; Høydahl, Lene Støkken; Christophersen, Asbjørn Otto; Risnes, Louise Fremgaard; Jahnsen, Jørgen & Lundin, Knut [Vis alle 8 forfattere av denne artikkelen] (2024). Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease. Cell reports. 43:114045(4), s. 1–23. doi: 10.1016/j.celrep.2024.114045. Fulltekst i vitenarkiv Vis sammendrag

  Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors. Unlike other IgA-switched cells, the TG2-specific cells are negative for CD27, placing them in the double-negative (IgD−CD27−) category. They have a plasmablast or activated memory B cell phenotype, and they harbor fewer variable region mutations than other IgA cells. Based on their similarity to naive B cells, we propose that autoreactive IgA cells in CeD are generated mainly through chronic recruitment of naive B cells via an extrafollicular response involving gluten-specific CD4+ T cells.

• Hatlen, Kristine Vaage; Lensnes, Therese Margrethe Lysell; Henriksen, Christine; Berg, Tore Julsrud; Nermoen, Ingrid & Lundin, Knut (2024). Suboptimal adherence to a gluten-free diet in adults with both type 1 diabetes and celiac disease using urinary gluten immunogenic peptide measurement. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 60(1), s. 28–36. doi: 10.1080/00365521.2024.2442688. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Concurrent type 1 diabetes (T1D) and celiac disease (CeD) pose challenges in insulin dosage adjustments and gluten-free dietary adherence. Urine testing for gluten immunogenic peptides (GIP) is a new method to detect gluten exposure within the last 3–12 h. Our aims were to compare gluten-free dietary adherence between T1D + CeD and CeD individuals and evaluate urinary GIP testing in an outpatient setting. Materials and methods This observational cross-sectional study included three adult groups: (1) T1D and CeD, (2) CeD only, and (3) T1D only. T1D participants were recruited from outpatient clinics, the CeD group via social media. One urine sample (12 pm–7 pm) was analyzed using a qualitative immunographic GIP test. CeD participants completed ‘Celiac Dietary Adherence Test’ (CDAT) and ‘Celiac Symptom Index’ (CSI) questionnaires. IgA anti-transglutaminase 2 (IgA-TG2) and IgG anti-deamidated gliadin (IgG-DGP) serology were also analyzed. Results 197 participants, mean (SD) age 43 (15) years, were included. Female percentages were: CeD: 90%, T1D + CeD: 64%, and T1D: 47%. Positive urinary GIP was found in 15% (14/96) of T1D + CeD and 0% (0/50) of CeD (p = 0.002). As expected, most T1D only participants had positive urinary GIP (86%, 44/51). CDAT and CSI scores did not differ between T1D + CeD and CeD groups. Positive IgA-TG2 and/or IgG-DGP levels were found in 12% of T1D + CeD and 6% of CeD participants (p = 0.38). Conclusions A single GIP urine test revealed higher gluten exposure in T1D + CeD versus CeD only, questioning dietary adherence in this population. Urinary GIP tests can be useful for clinical follow-up.

• Yang, Mingyi; Kaarbø, Mari; Myhre, Vegard; Reims, Henrik Mikael; Karlsen, Tom Hemming & Wang, Junbai [Vis alle 13 forfattere av denne artikkelen] (2024). Altered Genome-Wide DNA Methylation in the Duodenum of Common Variable Immunodeficiency Patients. Journal of Clinical Immunology. ISSN 0271-9142. 44(6), s. 1–16. doi: 10.1007/s10875-024-01726-5. Fulltekst i vitenarkiv Vis sammendrag

  Purpose A large proportion of Common variable immunodeficiency (CVID) patients has duodenal inflammation with increased intraepithelial lymphocytes (IEL) of unknown aetiology. The histologic similarities to celiac disease, lead to confusion regarding treatment (gluten-free diet) of these patients. We aimed to elucidate the role of epigenetic DNA methylation in the aetiology of duodenal inflammation in CVID and differentiate it from true celiac disease. Methods DNA was isolated from snap-frozen pieces of duodenal biopsies and analysed for differences in genome-wide epigenetic DNA methylation between CVID patients with increased IEL (CVID_IEL; n = 5) without IEL (CVID_N; n = 3), celiac disease (n = 3) and healthy controls (n = 3). Results The DNA methylation data of 5-methylcytosine in CpG sites separated CVID and celiac diseases from healthy controls. Differential methylation in promoters of genes were identified as potential novel mediators in CVID and celiac disease. There was limited overlap of methylation associated genes between CVID_IEL and Celiac disease. High frequency of differentially methylated CpG sites was detected in over 100 genes nearby transcription start site (TSS) in both CVID_IEL and celiac disease, compared to healthy controls. Differential methylation of genes involved in regulation of TNF/cytokine production were enriched in CVID_IEL, compared to healthy controls. Conclusion This is the first study to reveal a role of epigenetic DNA methylation in the etiology of duodenal inflammation of CVID patients, distinguishing CVID_IEL from celiac disease. We identified potential biomarkers and therapeutic targets within gene promotors and in high-frequency differentially methylated CpG regions proximal to TSS in both CVID_IEL and celiac disease.

• Herfindal, Anne Mari; Nilsen, Morten; Aspholm, Trude Elise; Schultz, Gry Irene Granli; Valeur, Jørgen & Rudi, Knut [Vis alle 10 forfattere av denne artikkelen] (2024). Effects of fructan and gluten on gut microbiota in individuals with self-reported non-celiac gluten/wheat sensitivity—a randomised controlled crossover trial. BMC Medicine. 22:358(1), s. 1–19. doi: 10.1186/s12916-024-03562-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Individuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved. Methods Our main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences). Results The relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (β-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline. Conclusions In conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms. Trial registration Clinicaltrials.gov as NCT02464150.

• Das, Saykat; Stamnæs, Jorunn; Høydahl, Lene Støkken; Skagen, Christine; Lundin, Knut & Jahnsen, Jørgen [Vis alle 8 forfattere av denne artikkelen] (2024). Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease. Journal of Autoimmunity. ISSN 0896-8411. 146, s. 1–10. doi: 10.1016/j.jaut.2024.103241. Fulltekst i vitenarkiv Vis sammendrag

  Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.

• Volta, Umberto; Rostami, Kamran; Auricchio, Renata & Lundin, Knut (2024). Diagnosis of Seronegative and Ultrashort Celiac Disease. Gastroenterology. ISSN 0016-5085. doi: 10.1053/j.gastro.2024.01.029. Fulltekst i vitenarkiv
• Kivelä, Laura; Lindfors, Katri; Lundin, Knut & Størdal, Ketil (2024). Review article: Faecal biomarkers for assessing small intestinal damage in coeliac disease and environmental enteropathy. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 60(8), s. 988–1004. doi: 10.1111/apt.18234. Fulltekst i vitenarkiv Vis sammendrag

  Background In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non-invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix. Aims To conduct a systematic literature search and summarize the existing evidence for host mucosa-derived faecal biomarkers in evaluating small intestinal damage. Methods We searched for studies on PubMed (MEDLINE) until 1 March 2024. Results We identified 494 studies and included 35 original case–control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell-mediated, innate and gluten-induced immune responses. In coeliac disease, faecal calprotectin and anti-gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β-defensin-2, lipocalin-2, zonulin-related proteins and angiotensin-converting enzyme. In environmental enteropathy, a non-significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet-derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy. Conclusions Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

• Elli, Luca; Leffler, Daniel; Cellier, Christophe; Lebwohl, Benjamin; Ciacci, Carolina & Schumann, Michael [Vis alle 28 forfattere av denne artikkelen] (2023). Guidelines for best practices in monitoring established coeliac disease in adult patients. Nature reviews: Gastroenterology & hepatology. ISSN 1759-5045. 0, s. 1–18. doi: 10.1038/s41575-023-00872-2. Fulltekst i vitenarkiv
• Gruper, Yael; Wolff, Anette Susanne Bøe; Glanz, Liad; Spoutil, Frantisek; Marthinussen, Ileana Mihaela Cuida & Osickova, Adriana [Vis alle 40 forfattere av denne artikkelen] (2023). Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease. Nature. ISSN 0028-0836. doi: 10.1038/s41586-023-06776-0. Fulltekst i vitenarkiv
• Lebwohl, Benjamin; Ma, Christopher; Lagana, Stephen M.; Pai, Rish K.; Baker, K. Adam & Zayadi, Alexa [Vis alle 25 forfattere av denne artikkelen] (2023). Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study. Gastroenterology. ISSN 0016-5085. doi: 10.1053/j.gastro.2023.08.051. Fulltekst i vitenarkiv
• Chlubnova, Marketa; Christophersen, Asbjørn Otto; Sandve, Geir Kjetil Ferkingstad; Lundin, Knut Erik Aslaksen; Jahnsen, Jørgen & Dahal-Koirala, Shiva [Vis alle 7 forfattere av denne artikkelen] (2023). Identification of gluten T cell epitopes driving celiac disease. Science Advances. 9(4), s. 1–8. doi: 10.1126/sciadv.ade5800. Fulltekst i vitenarkiv Vis sammendrag

  CD4+ T cells specific for cereal gluten proteins are key players in celiac disease (CeD) pathogenesis. While several CeD-relevant gluten T cell epitopes have been identified, epitopes recognized by a substantial proportion of gluten-reactive T cells remain unknown. The identification of such CeD-driving gluten epitopes is important for the food industry and in clinical settings. Here, we have combined the knowledge of a distinct phenotype of gluten-reactive T cells and key features of known gluten epitopes for the discovery of unknown epitopes. We tested 42 wheat gluten–reactive T cell clones, isolated on the basis of their distinct phenotype and with no reactivity to known epitopes, against a panel of synthetic peptides bioinformatically identified from a wheat gluten protein database. We were able to assign reactivity to 10 T cell clones and identified a 9-nucleotide oligomer core region of five previously uncharacterized gliadin/glutenin epitopes. This work represents an advance in the effort to identify CeD-driving gluten epitopes.

• Megen, Frida van; Fossli, Maria; Skodje, Gry Irene; Carlsen, Monica Hauger; Andersen, Lene Frost & Veierød, Marit Bragelien [Vis alle 8 forfattere av denne artikkelen] (2023). Nutritional assessment of women with celiac disease compared to the general population. Clinical Nutrition ESPEN. ISSN 2405-4577. 54, s. 251–257. doi: 10.1016/j.clnesp.2023.01.031. Fulltekst i vitenarkiv Vis sammendrag

  Background & aims The nutritional quality of a gluten-free diet is debated because of the elimination of grains that are important sources of nutrients. The aim of this cross-sectional study was to perform a nutritional assessment in treated women with celiac disease and ongoing symptoms, and compare dietary intake with a healthy reference group (Norkost 3). Methods Celiac disease patients with biopsy confirmed mucosal healing, but persistent gastrointestinal symptoms, were included from an ongoing clinical trial. Nutritional assessment included anthropometrics, blood samples and dietary intake obtained by two 24 h recalls. Dietary intake in celiac women was compared with dietary intake in healthy women (Norkost 3). Two sample t-test was used for comparison of CeD and Norkost 3 women. Adjustment for age, BMI, education and smoking, by use of multiple linear regression analysis, did not change the results. Results In total, 59 women with celiac disease and 925 women that participated in Norkost 3 were included, with a mean age of 45 years in both groups. Women with celiac disease had a higher proportion of energy (E%) from fat (39 vs 34%, P < 0.001) and saturated fat (15 vs 13%, P = 0.01), a lower E% from protein (16 vs 18%, P = 0.01) and a lower intake of dietary fiber (19 vs 22 g, P = 0.002) compared to Norkost 3 women. Women with celiac disease had a lower intake of bread, fruit and milk, and a higher intake of cereals and cheese compared to Norkost 3 women. The average requirement was not met for several micronutrients, but blood analysis revealed few nutritional deficiencies: two women with insufficient vitamin D status and one with insufficient folic acid status. Conclusion The women with celiac disease had an unbalanced diet with a higher intake of total- and saturated fatty acids and a lower intake of fiber compared to the general population. These findings emphasizes the need for nutritional follow-up of celiac patients and development of nutrient dense gluten-free products.

• Strahm, Noemi; Didriksen, Henriette; Fretheim, Håvard Halland; Molberg, Øyvind; Midtvedt, Øyvind & Farstad, Inger Nina [Vis alle 13 forfattere av denne artikkelen] (2023). Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis. Rheumatology. ISSN 1462-0324. 62(8), s. 2918–2929. doi: 10.1093/rheumatology/kead014. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objectives In SSc, gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling. Methods We analysed duodenal biopsies obtained pre-intervention (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving an intestinal infusion of FMT (n = 5) or placebo (n = 4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling. Results In patients receiving FMT, the number of podoplanin- and CD64-expressing cells in the mucosa were lower at week 2 compared with baseline. This decline in podoplanin- (r = 0.94) and CD64-positive (r = 0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T cell receptor complexes, and chemokine receptors, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16. Conclusion Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03444220.

• Das, Saykat; Stamnæs, Jorunn; Kemppainen, Esko; Hervonen, Kaisa; Lundin, Knut & Parmar, Naveen [Vis alle 12 forfattere av denne artikkelen] (2023). Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis. Advanced Science. 10:2300401(25), s. 1–10. doi: 10.1002/advs.202300401. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto‐antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto‐antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto‐antibodies are specific for either TG2 or TG3 with no TG2–TG3 cross reactivity. By generating monoclonal antibodies from TG3‐specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2‐specific and TG3‐specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase‐reactive populations show distinct selection of certain heavy and light chain V‐genes. Mass spectrometry analysis of TG3‐specific serum IgA corroborates preferential usage of IGHV2‐5 in combination with IGKV4‐1 . Collectively, these results demonstrate parallel induction of anti‐TG2 and anti‐TG3 auto‐antibody responses involving separate B‐cell populations in DH patients.

• Jørgensen, Kristin Kaasen; Høivik, Marte Lie; Chopra, Adity; Benth, Jurate Saltyte; Ricanek, Petr & Moum, Bjørn Allan [Vis alle 18 forfattere av denne artikkelen] (2023). Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), s. 874–882. doi: 10.1080/00365521.2023.2177884. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Materials and methods This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. Results In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Conclusions Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

• Garnweidner-Holme, Lisa; Hellmann, Monica; Henriksen, Christine; Austad, Elisabeh; Watters, Solveig Ivara Nakken & Gaundal, Line [Vis alle 9 forfattere av denne artikkelen] (2023). Experiences with Gluten-Free Bread: A Qualitative Study Amongst People with Coeliac Disease Participating in a Randomised Controlled Trial. Foods. 12:4338(23), s. 1–9. doi: 10.3390/foods12234338. Fulltekst i vitenarkiv Vis sammendrag

  Background: Whole-grain bread can be an important source of fibre for people with coeliac disease (CeD) who must adhere to a gluten-free diet and avoid consuming wheat, rye and barley. Gluten-free bread frequently has a lower nutritional quality and different texture relative to gluten-containing counterparts. Objective: The aim was to investigate experiences with gluten-free bread amongst people with CeD prior to and during a randomised controlled trial (RCT). Design: We conducted individual interviews with 10 people with CeD participating in a RCT that aimed to investigate the effects of fibre-rich gluten-free products on metabolic regulation in people with CeD compared with benchmark gluten-free products. Five participants were in the control group (benchmark gluten-free bread) and five participants in the intervention group (fibre-rich gluten-free bread). The fibre-rich gluten free bread was formulated and prepared by the project group. The benchmark gluten-free bread was commercially available. The RCT lasted for four weeks. Interviews were conducted digitally between October 2021 and January 2022 and were thematically analysed. Results: Participants in both groups appeared to avoid bread prior to the study, primarily due to the poor taste and chewy consistency of the available bread in food stores and bakeries. Participants preferred the fibre-rich intervention bread as opposed to the available bread in the food market. However, participants had to become accustomed to eating the fibre-rich whole-grain bread during the study, since they avoided eating store-bought bread that they experienced chewy and not filling. Conclusions: Participants asked for fibre-rich gluten-free bread products that are satiating and have a good texture. Palatable gluten-free bread products might be an important source of fibre for people with CeD.

• Chauhan, Sudhir Kumar; Casado, Raquel Bartolome; Landsverk, Ole J. B.; Johannessen, Hanna; Phung, Danh Thanh & Nilsen, Hogne Røed [Vis alle 14 forfattere av denne artikkelen] (2023). Human small intestine contains 2 functionally distinct regulatory T-cell subsets. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 152(1), s. 278–289.e6. doi: 10.1016/j.jaci.2023.02.030. Fulltekst i vitenarkiv Vis sammendrag

  Background Regulatory T (Treg) CD4 cells in mouse gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Treg cells in the human gut is limited. Objective We performed a detailed characterization of Foxp3+ CD4 Treg cells in human normal small intestine (SI) as well as from transplanted duodenum and celiac disease lesions. Methods Treg cells and conventional CD4 T cells derived from SI were subjected to extensive immunophenotyping and their suppressive activity and ability to produce cytokines assessed. Results SI Foxp3+ CD4 T cells were CD45RA−CD127−CTLA-4+ and suppressed proliferation of autologous T cells. Approximately 60% of Treg cells expressed the transcription factor Helios. When stimulated, Helios-negative Treg cells produced IL-17, IFN-γ, and IL-10, whereas Helios-positive Treg cells produced very low levels of these cytokines. By sampling mucosal tissue from transplanted human duodenum, we demonstrated that donor Helios-negative Treg cells persisted for at least 1 year after transplantation. In normal SI, Foxp3+ Treg cells constituted only 2% of all CD4 T cells, while in active celiac disease, both Helios-negative and Helios-positive subsets expanded 5- to 10-fold. Conclusion The SI contains 2 subsets of Treg cells with different phenotypes and functional capacities. Both subsets are scarce in healthy gut but increase dramatically in active celiac disease.

• Amundsen, Sunniva Furre; Stamnæs, Jorunn; Lundin, Knut & Sollid, Ludvig Magne (2023). Expression of transglutaminase 2 in human gut epithelial cells: Implications for coeliac disease. PLOS ONE. 18:e0287662(6), s. 1–15. doi: 10.1371/journal.pone.0287662. Fulltekst i vitenarkiv Vis sammendrag

  Background Formation of complexes between transglutaminase 2 (TG2) and gluten can mechanistically explain why TG2 serves both as B-cell autoantigen and as an enzyme that creates deamidated gluten epitopes in coeliac disease (CeD). A model has been proposed where TG2 released from shed epithelial cells encounters high concentrations of dietary gluten peptides to form these TG2:gluten complexes. In this work we have characterised TG2 protein expression in gut epithelial cells in humans. Methods Western blot analysis, immunofluorescence staining and mass spectrometry in combination with laser capture microdissection to gain spatial resolution were used to characterise TG2 expression in the epithelial cell layer of healthy and coeliac disease affected duodenum. Findings TG2 is expressed in human duodenal epithelial cells, including cells in the apical region that are shed into the gut lumen. In untreated CeD the apical expression of TG2 is doubled. Enzymatically active TG2 is readily released from isolated human intestinal epithelial cells. Conclusion Shed epithelial cells are a plausible source of pathogenic TG2 enzyme in CeD. Increased epithelial TG2 expression and increased epithelial shedding in active CeD may reinforce action of luminal TG2 in this condition.

• Herfindal, Anne Mari; Megen, Frida van; Gilde, Mari Kristine Overvik; Valeur, Jørgen; Rudi, Knut & Skodje, Gry [Vis alle 9 forfattere av denne artikkelen] (2023). Effects of a low FODMAP diet on gut microbiota in individuals with treated celiac disease having persistent gastrointestinal symptoms-a randomized controlled trial. British Journal of Nutrition. ISSN 0007-1145. 130(12), s. 2061–2075. doi: 10.1017/S0007114523001253. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD ( n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject β -diversity, P &lt; 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes ( P group &lt; 0·001) and class Erysipelotrichia ( P group = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline ( P interaction ≤ 0·009). No differences were found in faecal bacterial α -diversity ( P group ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation ( P group = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).

• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. 7(1). doi: 10.1038/s41541-022-00586-7. Fulltekst i vitenarkiv Vis sammendrag

  Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

• Skodje, Gry Irene; Megen, Frida van; Stendahl, Marianne; Henriksen, Christine; Lundin, Knut Erik Aslaksen & Veierød, Marit Bragelien (2022). Detection of gluten immunogenic peptides and the Celiac Disease Adherence Test to monitor gluten-free diet: a pilot study. European Journal of Clinical Nutrition. ISSN 0954-3007. 76. doi: 10.1038/s41430-021-01054-6. Fulltekst i vitenarkiv
• Megen, Frida van; Skodje, Gry Irene; Lergenmuller, Simon; Zühlke, Stephanie; Aabakken, Lars & Veierød, Marit Bragelien [Vis alle 8 forfattere av denne artikkelen] (2022). A low FODMAP diet reduces symptoms in treated celiac patients with ongoing symptoms–A randomized controlled trial. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 20(10), s. 2258–2266.E3. doi: 10.1016/j.cgh.2022.01.011. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet is an established treatment for irritable bowel syndrome (IBS). We have assessed the efficacy of a moderately low FODMAP diet on persistent symptoms in treated celiac patients. Methods A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)–IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. Participants were randomized to a low FODMAP–gluten-free diet (intervention) or usual gluten-free diet (control). The GSRS-IBS score was recorded at baseline and at weeks 1 to 4, and the Celiac Symptom Index at baseline and at week 4. Statistics included marginal models for repeated data and analyses of covariance. Results We included 34 participants in the intervention group and 36 in the control group. Time development of GSRS–IBS total scores differed significantly between the groups (Pinteraction < .001), evident after 1 week (mean difference in intervention vs control, -8.2; 95% CI, -11.5 to -5.0) and persisting through week 4 (mean difference in intervention vs control, -10.8; 95% CI, -14.8 to -6.8). Moreover, significantly lower scores were found for the dimensions of pain, bloating, diarrhea, and satiety (Pinteraction ≤ .04), but not constipation (Pinteraction = .43). FODMAP intake during the intervention was moderately low (mean, 8.1 g/d; 95% CI, 6.7–9.3 g/d). The Celiac Symptom Index was significantly lower in the intervention group at week 4 (mean difference, -5.8; 95% CI, -9.6 to -2.0). Conclusions A short-term moderately low FODMAP diet significantly reduced gastrointestinal symptoms and increased celiac disease–specific health, and should be considered for the management of persistent symptoms in celiac disease. ClinicalTrials.gov: NCT03678935.

• Ibsen, Jostein Holen; Chopra, Adity; Vaage, Eline Benno; Vaage, John T.; Lund-Johansen, Fridtjof & Lundin, Knut (2022). Immune responses to SARS-CoV-2 vaccines in celiac disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 00(0). doi: 10.1080/00365521.2022.2114809. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. Methods CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. Results Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). Conclusion The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.

• Christophersen, Asbjørn Otto; Dahal-Koirala, Shiva; Chlubnova, Marketa; Jahnsen, Jørgen; Lundin, Knut & Sollid, Ludvig Magne (2022). Phenotype-Based Isolation of Antigen-Specific CD4+ T Cells in Autoimmunity: A Study of Celiac Disease. Advanced Science. 9(10), s. 1–10. doi: 10.1002/advs.202104766. Fulltekst i vitenarkiv Vis sammendrag

  The pathogenic immune response in celiac disease (CeD) is orchestrated by phenotypically distinct CD4+ T cells that recognize gluten epitopes in the context of disease-associated HLA-DQ allotypes. Cells with the same distinct phenotype, but with elusive specificities, are increased across multiple autoimmune conditions. Here, whether sorting of T cells based on their distinct phenotype (Tphe cells) yields gluten-reactive cells in CeD is tested. The method′s efficiency is benchmarked by parallel isolation of gluten-reactive T cells (Ttet cells), using HLA-DQ:gluten peptide tetramers. From gut biopsies of 12 untreated HLA-DQ2.5+ CeD patients, Ttet+/Tphe+, Ttet−/Tphe+, and Ttet−/Tphe− cells are sorted for single-cell T-cell receptor (TCR)-sequencing (n = 8) and T-cell clone (TCC)-generation (n = 5). The generated TCCs are TCR sequenced and tested for their reactivity against deamidated gluten. Gluten-reactivity is observed in 91.2% of Ttet+/Tphe+ TCCs, 65.3% of Ttet−/Tphe+ TCCs and 0% of Ttet−/Tphe− TCCs. TCR sequencing reveals clonal expansion and sequence sharing across patients, features reflecting antigen-driven responses. The feasibility to isolate antigen-specific CD4+ T cells by the sole use of phenotypic markers in CeD outlines a potential avenue for characterizing disease-driving CD4+ T cells in autoimmune conditions.

• Klaasen, Rolf; Warren, David; Iversen, Rasmus; Bolstad, Nils; Andersen, Ina Lervåg & Mjønes, Patricia [Vis alle 10 forfattere av denne artikkelen] (2022). The development and validation of a high-capacity serological assay for celiac disease. Clinical Biochemistry. ISSN 0009-9120. 107, s. 13–18. doi: 10.1016/j.clinbiochem.2022.05.010. Fulltekst i vitenarkiv Vis sammendrag

  Background The aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease. Method An automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened. Subjects with serum anti-TG2 concentrations above a preliminary cut-off (>0.3 mg*/L anti-TG2 IgA or >0.5 mg*/L anti-TG2 IgG) were offered endoscopic examination and biopsy. A diagnosis of celiac disease was given if villous atrophy (Marsh grade 3) was found. Results The assay had a limit of quantification of 0.25 mg*/L (anti-TG2 IgA) and 0.60 mg*/L (anti-TG2 IgG) with imprecision (CV) < 16% and <18% respectively. A total of 66 individuals were above the preliminary cut-off, and 56 underwent endoscopy. Of these, 26 were diagnosed with celiac disease. Sixty-eight percent of subjects with anti-TG2 IgA ≥ 0.7 mg*/L or anti-TG2 IgG ≥ 1.0 mg*/L had biopsy-proven celiac disease, and utilization of these higher cut-offs identified 96% of biopsy-positive patients. At the time of endoscopy, all individuals with anti-TG2 IgA > 2.0 mg*/L had celiac disease, and this cut-off identified 88% of newly diagnosed celiac patients. Eight percent (2/26) of the newly diagnosed patients had primarily anti-TG2 IgG. Conclusions In this study we developed and clinically validated a robust and automated assay suitable for celiac disease screening in the general population.

• Dahal-Koirala, Shiva; Balaban, Gabriel; Neumann, Ralf Stefan; Scheffer, Lonneke; Lundin, Knut & Greiff, Victor [Vis alle 9 forfattere av denne artikkelen] (2022). TCRpower: quantifying the detection power of T-cell receptor sequencing with a novel computational pipeline calibrated by spike-in sequences. Briefings in Bioinformatics. ISSN 1467-5463. 23(2), s. 1–14. doi: 10.1093/bib/bbab566. Fulltekst i vitenarkiv Vis sammendrag

  T-cell receptor (TCR) sequencing has enabled the development of innovative diagnostic tests for cancers, autoimmune diseases and other applications. However, the rarity of many T-cell clonotypes presents a detection challenge, which may lead to misdiagnosis if diagnostically relevant TCRs remain undetected. To address this issue, we developed TCRpower, a novel computational pipeline for quantifying the statistical detection power of TCR sequencing methods. TCRpower calculates the probability of detecting a TCR sequence as a function of several key parameters: in-vivo TCR frequency, T-cell sample count, read sequencing depth and read cutoff. To calibrate TCRpower, we selected unique TCRs of 45 T-cell clones (TCCs) as spike-in TCRs. We sequenced the spike-in TCRs from TCCs, together with TCRs from peripheral blood, using a 5′ RACE protocol. The 45 spike-in TCRs covered a wide range of sample frequencies, ranging from 5 per 100 to 1 per 1 million. The resulting spike-in TCR read counts and ground truth frequencies allowed us to calibrate TCRpower. In our TCR sequencing data, we observed a consistent linear relationship between sample and sequencing read frequencies. We were also able to reliably detect spike-in TCRs with frequencies as low as one per million. By implementing an optimized read cutoff, we eliminated most of the falsely detected sequences in our data (TCR α-chain 99.0% and TCR β-chain 92.4%), thereby improving diagnostic specificity. TCRpower is publicly available and can be used to optimize future TCR sequencing experiments, and thereby enable reliable detection of disease-relevant TCRs for diagnostic applications.

• Kaarbø, Mari; Yang, Mingyi; Hov, Johannes Espolin Roksund; Holm, Kristian; Sousa, Mirta & Macpherson, Magnhild Eide [Vis alle 15 forfattere av denne artikkelen] (2022). Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. doi: 10.1016/j.jaci.2022.09.029. Fulltekst i vitenarkiv Vis sammendrag

  Background A substantial proportion of common variable immunodeficiency (CVID) patients has duodenal inflammation of largely unknown etiology. However, because of its histologic similarities with celiac disease, gluten sensitivity has been proposed as a potential mechanism. Objective We aimed to elucidate the role of the duodenal microenvironment in the pathogenesis of duodenal inflammation in CVID by investigating the transcriptional, proteomic, and microbial signatures of duodenal biopsy samples in CVID. Methods DNA, total RNA, and protein were isolated from snap-frozen pieces of duodenal biopsy samples from CVID (with and without duodenal inflammation), healthy controls, and patients with celiac disease (untreated). RNA sequencing, mass spectrometry–based proteomics, and 16S ribosomal DNA sequencing (bacteria) were then performed. Results CVID separated from controls in regulation of transcriptional response to lipopolysaccharide and cellular immune responses. These differences were independent of mucosal inflammation. Instead, CVID patients with duodenal inflammation displayed alterations in transcription of genes involved in response to viral infections. Four proteins were differently regulated between CVID patients and healthy controls—DBNL, TRMT11, GCHFR, and IGHA2—independent of duodenal inflammation. Despite similar histology, there were major differences in CVID with duodenal inflammation and celiac disease both at the RNA and protein level. No significant difference was observed in the bacterial gut microbial signature between CVID, celiac, and healthy controls. Conclusion Our findings suggest the existence of altered functions of the duodenal epithelium, particularly in response to lipopolysaccharide and viruses. The latter finding was related to duodenal inflammation, suggesting that viruses, not gluten sensitivity, could be related to duodenal inflammation in CVID. Key words CVID RNA sequencing proteomics microbiome gut microbiota microbiota gastrointestinal tract duodenum celiac disease Primary immunodeficiency IgA

Se alle arbeider i NVA

• Lundin, Knut; Sarna, Vikas Kumar & Ness-Jensen, Eivind (2026). Blodprøvebasert cøliakidiagnostikk hos voksne – nye retningslinjer! Indremedisineren. ISSN 1891-1617. s. 36–37. doi: https:/indremedisineren.no/2026/09/blodprovebasert-coliakidiagnostikk-hos-voksne-nye-retningslinjer/. Fulltekst i vitenarkiv
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Haug, Eirin Beate [Vis alle 10 forfattere av denne artikkelen] (2026). Traditional risk factors underestimate cardiovascular risk in individuals with coeliac disease in the Trondelag Health Study (HUNT4). European Heart Journal. ISSN 0195-668X. 47. Fulltekst i vitenarkiv
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Vis alle 10 forfattere av denne artikkelen] (2026). Kardiovaskulær risiko hos individer med cøliaki i HUNT4. Fulltekst i vitenarkiv
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Vis alle 10 forfattere av denne artikkelen] (2025). CARDIOVASCULAR RISK IN INDIVIDUALS WITH COELIAC DISEASE IN THE TRØNDELAG HEALTH STUDY (HUNT4). United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 13(S8), s. 483–484. doi: https:/onlinelibrary.wiley.com/toc/20506414/2025/13/S8. Fulltekst i vitenarkiv
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Vis alle 10 forfattere av denne artikkelen] (2025). Cardiovascular Risk in Individuals with Coeliac Disease in the Trøndelag Health Study (HUNT4). Fulltekst i vitenarkiv
• Risnes, Louise Fremgaard; Dahal-Koirala, Shiva; Hjort, Rebecka; Bolstad, Nils; Lundin, Knut & Ness-Jensen, Eivind [Vis alle 7 forfattere av denne artikkelen] (2025). Detection of gluten-specific CD4+ T cells with tetramer test among anti-transglutaminase seropositive participants in the HUNT4 study. Fulltekst i vitenarkiv
• Hjort, Rebecka; Asefa, Tesfaye Mandefro; Lukina, Polina; Andersen, Ina Lervåg; Carlsson, Sofia & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2025). Prevalence of autoimmune diabetes and thyroid dysfunction in adults screened for celiac disease – Insights from the population-based HUNT Study. Fulltekst i vitenarkiv
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Vis alle 10 forfattere av denne artikkelen] (2025). Cardiovascular Risk in Individuals with Coeliac Disease in the Trøndelag Health Study (HUNT4). Hjerteforum. ISSN 0802-1465. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies indicate an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and guidelines on the management of CVD risk for individuals with CeD do not exist. Here, we compare the distribution of CVD risk factors in CeD patients and non-CeD controls from a population-based cohort. Methods: We performed an anti-transglutaminase-2-based CeD screening of 54,541 serum samples from adult participants in HUNT4 [4]. Seropositive participants were invited to gastroscopy for diagnosis confirmation. Seronegative participants with CeD were identified by linkage of hospital records and the Norwegian Patient Registry. We calculated SCORE2(-OP) and analysed samples for lipoprotein (a), NTproBNP, FGF-23, IL-6, IL1RL1/ST2 and GDF-15 [5-9]. Individuals with a previous diagnosis (“known CeD”), CeD diagnosed in HUNT4 (“new CeD”), as well as the combination of the two subgroups (“CeD”) were compared to non-CeD controls (“no CeD”). Results: 468 (0.8%) individuals received a CeD diagnosis in HUNT4, while 309 (0.6%) seronegative individuals had known CeD. Newly diagnosed individuals are younger, better educated, and have lower blood lipids compared to controls. Individuals with CeD have smoked less, have a lower BMI, lower HbA1c, serum creatinine, and hsCRP levels compared to controls. NORRISK2 and SCORE2 are lower in CeD cases (p<0.05 for all variables mentioned, see Table). Lipoprotein (a) does not differ between groups, while NTproBNP is increased in individuals with known CeD (484 vs. 566 pg/mL, p<0.05) compared to newly diagnosed ones. Individuals with CeD have higher levels of GDF-15 in serum. Conclusions: Individuals with CeD have a lower CVD risk compared to controls. In line with that, both NORRISK2 and SCORE2(-OP) were lower. However, GDF-15, an emerging biomarker of cellular stress and inflammation associated with nonischemic scars [7, 9], is upregulated in individuals with CeD.

• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Vis alle 10 forfattere av denne artikkelen] (2025). CARDIOVASCULAR RISK IN INDIVIDUALS WITH COELIAC DISEASE IN THE TRØNDELAG HEALTH STUDY (HUNT4). Fulltekst i vitenarkiv
• Ness-Jensen, Eivind & Lundin, Knut (2024). Cøliaki-funn vekker oppsikt. [Journal]. Dagbladet. Fulltekst i vitenarkiv
• Hjort, Rebecka Louise; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). MAPPING OF HLA-DQ HAPLOTYPES IN ADULTS WITH COELIAC DISEASE IN A LARGE, SCREENED POPULATION – RESULTS FROM THE HUNT STUDY. Fulltekst i vitenarkiv
• Hjort, Rebecka Louise; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). MAPPING OF HLA-DQ HAPLOTYPES IN ADULTS WITH COELIAC DISEASE IN A LARGE, SCREENED POPULATION – RESULTS FROM THE HUNT STUDY. Gastroenterology. ISSN 0016-5085. 166(5), s. S-728–S-728. Fulltekst i vitenarkiv
• Hjort, Rebecka Louise; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). Mapping of HLA-DQ haplotypes in adults with coeliac disease in a large, screened population – results from the HUNT Study. Fulltekst i vitenarkiv
• Alam, Mohammad Sayeef; Hjort, Rebecka Louise; Hveem, Kristian; Lundin, Knut; Jonkers, Iris H. & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). Assessing the susceptibility of celiac disease by polygenic risk scores: analysis of a population-based cohort, the HUNT study. Fulltekst i vitenarkiv
• Alam, Mohammad Sayeef; Hjort, Rebecka Louise; Thomas, Laurent Francois; Brumpton, Ben Michael; Hveem, Kristian & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2024). The IRX1 locus is associated with celiac disease: results from a screened population-based cohort, the HUNT study. Fulltekst i vitenarkiv
• Rosman, Mari; Lundin, Knut & Valeur, Jørgen (2024). Tarmen din lekker. [Journal]. Fordøyelsen. Fulltekst i vitenarkiv
• Alam, Mohammad Sayeef; Hjort, Rebecka Louise; Hveem, Kristian; Lundin, Knut; Jonkers, Iris H. & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). Assessing the susceptibility of celiac disease by polygenic risk scores: analysis of a population-based cohort, the HUNT study. Fulltekst i vitenarkiv
• Alam, Mohammad Sayeef; Hjort, Rebecka Louise; Thomas, Laurent Francois; Brumpton, Ben Michael; Hveem, Kristian & Lundin, Knut [Vis alle 9 forfattere av denne artikkelen] (2024). The IRX1 locus is associated with celiac disease: results from a screened population-based cohort, the HUNT study. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf; Warren, David John; Bolstad, Nils & Sollid, Ludvig Magne [Vis alle 8 forfattere av denne artikkelen] (2024). Serological signs of coeliac disease in pre-diagnostic samples from a population-based cohort of coeliacs, the Trøndelag Health Study (HUNT), Norway. Fulltekst i vitenarkiv
• Risnes, Louise Fremgaard; Dahal-Koirala, Shiva; Hjort, Rebecka Louise; Bolstad, Nils; Christophersen, Asbjørn Otto & Sarna, Vikas Kumar [Vis alle 9 forfattere av denne artikkelen] (2024). Påvisning av glutenspesifikke CD4+ T-celler med tetramertest blant anti-transglutaminase seropositive deltakere i HUNT4-studien. Fulltekst i vitenarkiv
• Melby, Kjetil Klaveness; Hjort, Rebecka Louise; Lundin, Knut & Ness-Jensen, Eivind (2024). POSSIBLE INTERFERENCE OF INFECTION WITH HELICOBACTER PYLORI WITH THE ONSET OF COELIAC DISEASE. Fulltekst i vitenarkiv
• Hjort, Rebecka; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). MAPPING OF HLA-DQ HAPLOTYPES IN ADULTS WITH COELIAC DISEASE IN A LARGE, SCREENED POPULATION – RESULTS FROM THE NORWEGIAN HUNT STUDY. Fulltekst i vitenarkiv
• Hjort, Rebecka; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). Mapping of HLA-DQ haplotypes in adults with coeliac disease in a large, screened population – results from the Norwegian HUNT study. Fulltekst i vitenarkiv
• Hjort, Rebecka; Andersen, Ina Lervåg; Lukina, Polina; Hveem, Kristian; Lundin, Knut & Sollid, Ludvig Magne [Vis alle 7 forfattere av denne artikkelen] (2024). Mapping of HLA-DQ haplotypes in adults with coeliac disease in a large, screened population – results from the Norwegian HUNT study. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf; Warren, David John; Bolstad, Nils & Iversen, Rasmus [Vis alle 9 forfattere av denne artikkelen] (2024). Serologiske tegn på cøliaki i pre-diagnostiske prøver fra en populasjonsbasert kohort av voksne cøliakere, Helseundersøkelsen i Trøndelag (HUNT). Fulltekst i vitenarkiv
• Dyrli, Ole Thomas; Andersen, Ina Lervåg; Lukina, Polina; Klaasen, Rolf; Bolstad, Nils & Warren, David John [Vis alle 9 forfattere av denne artikkelen] (2024). Anti-transglutaminase 2 immunoglobulin G in population-based screening for coeliac disease, the Trøndelag Health Study, Norway. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 12, s. 11–12. Fulltekst i vitenarkiv
• Dyrli, Ole Thomas; Andersen, Ina Lervåg; Lukina, Polina; Klaasen, Rolf; Bolstad, Nils & Warren, David John [Vis alle 9 forfattere av denne artikkelen] (2024). Anti-transglutaminase 2 immunoglobulin G in population-based screening for coeliac disease, the Trøndelag Health Study, Norway. Fulltekst i vitenarkiv
• Bostrøm, Stine; Uthaug, Lindis; Hjort, Rebecka Louise; Andersen, Ina Lervåg; Lukina, Polina & Sollid, Ludvig Magne [Vis alle 8 forfattere av denne artikkelen] (2024). Endoscopic findings in coeliac disease identified through population-based screening, the Trøndelag Health Study, Norway. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 12, s. 612–612. Fulltekst i vitenarkiv
• Bostrøm, Stine; Uthaug, Lindis; Hjort, Rebecka Louise; Andersen, Ina Lervåg; Lukina, Polina & Sollid, Ludvig Magne [Vis alle 8 forfattere av denne artikkelen] (2024). Endoscopic findings in coeliac disease identified through population-based screening, the Trøndelag Health Study, Norway. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Bolstad, Nils & Sollid, Ludvig Magne [Vis alle 8 forfattere av denne artikkelen] (2023). SEROLOGICAL SIGNS OF COELIAC DISEASE IN PRE-DIAGNOSTIC SAMPLES FROM A POPULATION-BASED COHORT OF COELIACS, THE TRØNDELAG HEALTH STUDY (HUNT), NORWAY. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 11. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Iversen, Rasmus & Mjønes, Patricia Gjertrud [Vis alle 11 forfattere av denne artikkelen] (2023). THE TOTAL PREVALENCE AND RATE OF UNDIAGNOSED CELIAC DISEASE IN AN ADULT GENERAL POPULATION – THE HUNT STUDY, NORWAY. Gastroenterology. ISSN 0016-5085. 164(6), s. S-218–S-218. Fulltekst i vitenarkiv
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. 8(1). doi: 10.1038/s41541-023-00600-6. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David J; Bolstad, Nils & Mjønes, Patricia Gjertrud [Vis alle 11 forfattere av denne artikkelen] (2023). Prevalensen av cøliaki i den generelle befolkningen (HUNT4). Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Iversen, Rasmus & Mjønes, Patricia Gjertrud [Vis alle 11 forfattere av denne artikkelen] (2023). THE TOTAL PREVALENCE AND RATE OF UNDIAGNOSED CELIAC DISEASE IN AN ADULT GENERAL POPULATION – THE HUNT STUDY, NORWAY. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Bolstad, Nils & Sollid, Ludvig Magne [Vis alle 8 forfattere av denne artikkelen] (2023). SEROLOGICAL SIGNS OF COELIAC DISEASE IN PRE-DIAGNOSTIC SAMPLES FROM A POPULATION-BASED COHORT OF COELIACS, THE TRØNDELAG HEALTH STUDY (HUNT), NORWAY. Fulltekst i vitenarkiv
• Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Lukina, Polina; Mjønes, Patricia & Rønne, Elin [Vis alle 11 forfattere av denne artikkelen] (2022). Screening for adult celiac disease in the general population. Gastroenterology. ISSN 0016-5085. 162(7), s. S-353–S-353. Fulltekst i vitenarkiv
• Klaasen, Rolf; Warren, David; Iversen, Rasmus; Bolstad, Nils; Andersen, Ina Lervåg & Mjønes, Patricia [Vis alle 10 forfattere av denne artikkelen] (2022). THE DEVELOPMENT AND VALIDATION OF A HIGH CAPACITY SEROLOGICAL ASSAY FOR CELIAC DISEASE. Fulltekst i vitenarkiv
• Andersen, Ina Lervåg; Klaasen, Rolf Anton; Warren, David; Lukina, Polina; Mjønes, Patricia & Rønne, Elin [Vis alle 11 forfattere av denne artikkelen] (2022). Screening for adult celiac disease in the general population. Fulltekst i vitenarkiv
• Klaasen, Rolf; Warren, David; Iversen, Rasmus; Bolstad, Nils; Andersen, Ina Lervåg & Mjønes, Patricia [Vis alle 10 forfattere av denne artikkelen] (2022). THE DEVELOPMENT AND VALIDATION OF A HIGH CAPACITY SEROLOGICAL ASSAY FOR CELIAC DISEASE. Gastroenterology. ISSN 0016-5085. 162(7), s. S-359–S-359. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Klaasen, Rolf; Warren, David; Iversen, Rasmus & Mjønes, Patricia [Vis alle 11 forfattere av denne artikkelen] (2022). THE PREVALENCE OF COELIAC DISEASE IN THE UNSELECTED GENERAL POPULATION. Fulltekst i vitenarkiv
• Melby, Kjetil Klaveness; Lundin, Knut & Ness-Jensen, Eivind (2022). Possible interference of infection with Helicobacter pylori with the onset of coeliac disease. Fulltekst i vitenarkiv
• Lukina, Polina; Andersen, Ina Lervåg; Hjort, Rebecka; Eggen, Petter Tinbod; Næss, Marit & Mjønes, Patricia [Vis alle 20 forfattere av denne artikkelen] (2022). Cøliaki i HUNT. Forekomst, konsekvenser og årsaker. Fulltekst i vitenarkiv
• Andersen, Ina Lervåg; Klaasen, Rolf; Warren, David; Lukina, Polina; Mjønes, Patricia & Rønne, Elin [Vis alle 11 forfattere av denne artikkelen] (2022). Screening for cøliaki i den voksne befolkningen. Fulltekst i vitenarkiv
• Klaasen, Rolf; Warren, David; Iversen, Rasmus; Bolstad, Nils; Andersen, Ina Lervåg & Mjønes, Patricia [Vis alle 10 forfattere av denne artikkelen] (2022). The development and validation of a high-capacity serological assay for coeliac disease. Fulltekst i vitenarkiv
• Andersen, Ina Lervåg; Ness-Jensen, Eivind & Lundin, Knut (2026). Prevalence and screening of coeliac disease. A prospective population-based cohort study: The HUNT study. NTNU Norges teknisk-naturvitenskapelige universitet. ISSN 9788235304445. Vis sammendrag

  Forekomst og screening av cøliaki Cøliaki er en kronisk immunmediert sykdom med dannelse av antistoffer mot enzymet transglutaminase. Når gluten fra matvarer inntas, kan dette gi en kronisk betennelse i slimhinnen i tolvfingertarmen. Tilstanden kan gi symptomer fra mage-tarm kanalen slik som oppblåsthet og løs avføring, men kan også gi symptomer fra andre organsystemer. Betennelsen kan medføre dårlig opptak av næringsstoffer fra tarmen, noe som kan føre til mangel på blant annet jern og vitaminer. Ubehandlet kan cøliaki hos enkelte individer gi økt risiko for en rekke tilstander, blant annet kreft. Cøliaki har høy forekomst i hele verden, men spesielt i Nord-Europa, og det er en høy andel av udiagnostiserte pasienter. Forekomsten ser ut til å være økende. Diagnosen cøliaki hos voksne stilles baserte på nivået av antistoffer mot transglutaminase i blodprøver og funn på vevsprøver tatt ved gastroskopi fra tolvfingertarmen. Hos barn kan diagnosen stilles uten gastroskopi dersom antistoffnivået er høyt nok i to prøver (over 10 ganger øvre normalområde). De nye europeiske retningslinjene for cøliaki for voksne åpner nå opp for at man kan stille diagnosen uten vevsprøver også hos voksne under 45 år, gitt visse kriterier. I denne studien ønsket vi å finne den den totale forekomsten av cøliaki i en generell norsk befolkning, både de med kjent cøliaki og de udiagnostiserte. Videre ønsket vi å undersøke hvor gode antistoffene mot transglutaminase er til å diagnostisere cøliaki gjennom blodprøvescreening av den generelle befolkningen. Til slutt ønsket vi å undersøke hvilke tilleggsfunn som ble gjort ved den diagnostiske gastroskopien, for å avklare tilleggsnytten av å påvise andre klinisk relevante funn. I den fjerde Helseundersøkelsen i Nord-Trøndelag (HUNT4) ble 54505 voksne over 20 år screenet for cøliaki med blodprøve og en kombinert antistofftest mot transglutaminase IgA og IgG. Alle deltagerne med positiv blodprøve ble invitert til videre undersøkelser med blant annet nye blodprøver og gastroskopi med biopsier i tolvfingertarmen for å bekrefte diagnosen og registrere tilleggsfunn ved gastroskopi. Den totale forekomsten av cøliaki i befolkningen ble undersøkt ved å registrere deltagerne hvor det ble påvist cøliaki gjennom HUNT4, samt gjennom å finne de deltagerne med allerede kjent cøliaki med hjelp av registersøk. Av alle 54505 HUNT4-deltagerne med tilgjengelig blodprøve hadde 2% (1107/54505) positive antistoff mot transglutaminase. Blant disse fikk 470 deltagere bekreftet diagnosen i vevsprøvene. I tillegg hadde 383 deltakere en kjent cøliaki-diagnose. Den totale forekomsten av cøliaki bekreftet med vevsprøver var 1,5 % (853/56042) og forholdet mellom nye, tidligere udiagnostiserte cøliakere (etter HUNT4) mot kjente, tidligere diagnostiserte cøliakere var 1,2:1 (470/383). Positiv prediktiv verdi er sannsynligheten for at en person med positivt testresultat har sykdommen som det ble testet for [1]. Positiv prediktiv verdi for cøliaki bekreftet med vevsprøver ved positiv transglutaminase IgA var 73,3 %. Positiv prediktiv verdi ved 10 ganger øvre normalområde (som ved diagnostisering av barn) var 88,1 %. Positiv prediktiv verdi ved positiv transglutaminase IgG var derimot kun 5,8 %, og ved 10 ganger øvre normal 9,5 % for cøliaki bekreftet med vevsprøver. Rundt 30 % av deltagerne hadde minst ett endoskopisk tilleggsfunn. Kun to deltagere hadde forstadier til kreftsykdom (Barretts øsofagus, magesår eller adenomer), men dette ble bare funnet hos deltagere over 60 år. Risikoen for tilleggsfunn økte med økende alder, var høyere blant menn og hos deltagere som brukte betennelsesdempende eller syrehemmende medikamenter. Studien bekrefter at cøliaki har høy forekomst og at mange har diagnosen uten å vite det. Antistoff mot transglutaminase IgA hadde høy positiv prediktiv verdi og fungerte godt som et screeningverktøy for cøliaki i en generell befolkning. Risikoen for å overse kliniske relevante endoskopiske tilleggsfunn er lav hos voksne under 60 år. Disse funnene støtter en diagnostisk tilnærming for cøliaki uten gastroskopi hos yngre voksne.

• Alam, Mohammad Sayeef; Ness-Jensen, Eivind; Hjort, Rebecka; Sollid, Ludvig Magne & Lundin, Knut (2026). The genetic and environmental susceptibility for celiac disease. Norges teknisk-naturvitenskapelige universitet. ISSN 9788232698332. Fulltekst i vitenarkiv Vis sammendrag

  Celiac disease (CeD) is a lifelong immune-mediated condition that affects genetically susceptible individuals worldwide and is triggered by consuming gluten, a protein found in wheat, rye, and barley. It presents with a wide range of symptoms, from mild gastrointestinal complaints like bloating, constipation and stomach pain to severe complications such as anemia, osteoporosis, and infertility. Among adults, atypical symptoms like fatigue, brain fog, and mental distress are more common, leading to misdiagnosis or remaining undiagnosed, contributing to the iceberg like nature of CeD. In Norway, biopsy-confirmed diagnosis is double the global average, with 55% of these being previously undiagnosed. Fortunately, awareness of the disease and advancements in diagnostic technologies have led to increasing detection rates in recent studies. Currently, the only treatment is strict adherence to a gluten-free diet. The Trøndelag Health Study (HUNT4), conducted between 2017 and 2019 in Nord-Trøndelag County, Norway, invited 103,000 adults (aged ≥20 years) to participate. A total of 56,042 individuals participated, 54.6% of whom were women. HUNT is a unique longitudinal database of questionnaire data, clinical measurements and samples from the county’s inhabitants from 1984. From HUNT2 onwards, all biological samples were genotyped, providing a rich resource of genetic data. From HUNT4, 826 individuals were identified as biopsy-confirmed eD, of these 361 were identified through hospital-based medical journal searches, and 465 individuals were newly diagnosed. With genetic information, also available for all individuals from HUNT4, we performed genome-wide association analysis, polygenic risk scoring for comparison between the two groups, and finally tested a clinical prediction model corporating genetics, lifestyle, symptoms, comorbidities, and biomarkers to aid clinicians. A novel locus in a non-protein-coding region (5p15.33) was identified, adding to the 42 previously known loci. On average, individuals with CeD had a PRS of 1.7 units, placing them at 3.5 times higher risk compared to the general population. The previously known cases and newly diagnosed cases were comparable based on the genetic risk load that carry both at an aggregated PRS level as well as at variant level. PRS had a slightly higher (comparable) discriminatory power compared to the HLA haplotypes. Finally, clinical aid achieved high discrimination between cases and healthy individuals. The model at low predicted risk probability was able to capture more actual cases compared to general population screening. In conclusion, this thesis sets out to explore the genetic and environmental underpinnings of celiac disease in a large, population-based cohort, and it has yielded several important findings. The study confirmed that genetic variants associated with CeD are not limited to protein-coding or immune-specific regions, highlighting the relevance of non-coding loci such as 5p15.33. It also demonstrated that both newly detected and previously undiagnosed individuals carry similar genetic risk, distinguishing them from non-cases. By leveraging polygenic risk scores, the study established a strong association between genetic predisposition and CeD. The combination of genetic and non-genetic factors further enhances case detection at true population prevalence settings. The study is limited with lack of external validation for the genetic findings as well as for the clinical prediction model. Future studies require more ethnically diverse population, with longitudinal information on environmental factors to determine causal pathways outside genetics. This would enhance the understanding the disease and prevent and manage the disease better.

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