Jorunn Stamnæs

• Gildenblat, Jacob; Stamnæs, Jorunn & Pahnke, Jens (2025). Mass-spectrometry imaging-based explainable machine learning can be used to reveal biochemical landscapes of the brain. BioaRxiv. doi: 10.1101/2025.09.12.675752. Full text in Research Archive Show summary

  Abstract Recent computational advances in mass-spectrometry imaging (MSI) now enable unprecedented insight into organ-wide molecular composition and functional architecture. Here, we present a first example of a high-resolution, molecular-computational atlas of specific mouse brain lipids - acquired using a NEDC matrix and negative mode MSI - covering 123 anatomically defined regions with 191 polygonal annotations derived solely from the MSI data — no auxiliary imaging required. To overcome annotation ambiguity and MSI complexity, we introduced the Computational Brain Lipid Atlas (CBLA), a graph-based visual-explainability framework that generates virtual landscape visualizations (VLV) of specific lipids’ distributions across the brain substructures. The CBLA integrates dimensionality reduction and ensembles of supervised models to (i) refine annotations, (ii) elucidate interregional relationships, (iii) interpret model behavior, and (iv) formulate biologically testable hypotheses. The CBLA revealed novel lipid distribution patterns, functional integrations, anatomical connections - ’the brain’s telephone cables’, and region-specific disease signatures - disease networks in the basal ganglia. A new algorithm decomposes annotated regions into precise m/z features and resolves full-precision m/z values from MSI data, producing a comprehensive high-resolution brain map. It can be used for any MS measurements: metabolites, lipids, and peptides. This resource underpins downstream studies, exemplified here by characterizing the lipid molecular composition of A β plaques, their spatial arrangement, and their connections with the surrounding tissue. Highlights Mass Spectrometry Imaging (MSI) data were used to generate truthful visualizations for annotating brain regions with high resolution without the need for other modalities. MSI data were used to generate a computational atlas representation of the annotated brain regions. Pathological structures reveal their origin and their effects on specific brain networks. Anatomical regions and functional networks show specific lipid patterns. Brain stem nuclei and the white matter have a unique composition of lipids revealing their involvement in pathological networks. The atlas’ Virtual Landscape Visualizations (VLV) enable visualizing region-specific differences between different mouse models.

• Stamnæs, Jorunn; Stray, Daniel; Pré, Marie Fleur du; Risnes, Louise Fremgaard; Dewan, Alisa & Shaik, Jakeer [Show all 9 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Johansen, Anette; Sandve, Geir Kjetil Ferkingstad; Maxwell, Joseph R.; Smithson, Glennda; Sollid, Ludvig Magne & Stamnæs, Jorunn (2024). Biopsy Proteome Score Performs Well as an Effect Measure in a Gluten Challenge Trial of Celiac Disease. Clinical Gastroenterology and Hepatology. ISSN 1542-3565. 23(5), p. 758–765.e8. doi: 10.1016/j.cgh.2024.08.005. Full text in Research Archive Show summary

  Background and Aims Development of novel treatments for celiac disease is dependent on precise tools to monitor changes in gluten-induced mucosal damage. Current histology measures are subjective and difficult to standardize. Biopsy proteome scoring is an objective alternative to histology which is based on robust changes in biological pathways that directly reflect gluten-induced mucosal damage. In this study, we aimed to evaluate biopsy proteome scoring as an effect measure in a clinical trial setting by measuring intestinal remodeling in response to oral gluten challenge. Methods We analyzed biopsies from a 14-day gluten challenge trial of treated celiac disease patients that consumed 3 g (n = 6) or 10 g (n = 7) gluten per day. Sections from individually embedded biopsies collected before and after challenge were processed for proteome scoring (n = 109) and measurement of villus height-to-crypt depth ratio (n = 58). Proteome scores were compared with histology, intraepithelial lymphocyte frequency and plasma interleukin-2. Results Change in proteome scores were significant for the group of patients who consumed 10 g gluten, but not for the group who consumed 3 g gluten. Altogether, 8 of 13 patients had changes in delta proteome scores above the cutoff. Proteome scores correlated with villus height-to-crypt depth ratios both at run-in and at day 15. Proteome scores at day 15 correlated with intraepithelial lymphocyte frequency and with plasma interleukin-2 levels measured 4 hours post–gluten intake. Conclusion Biopsy proteome scoring is a simple and reliable measure of gluten-induced mucosal remodeling in response to 14-day oral gluten challenge. ClinicalTrials.gov, Number: NCT03409796.

• 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), p. 493–504. doi: 10.1053/j.gastro.2024.03.006. Full text in Research Archive Show summary

  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.

• Das, Saykat; Stamnæs, Jorunn; Høydahl, Lene Støkken; Skagen, Christine; Lundin, Knut & Jahnsen, Jørgen [Show all 8 contributors for this article] (2024). Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease. Journal of Autoimmunity. ISSN 0896-8411. 146, p. 1–10. doi: 10.1016/j.jaut.2024.103241. Full text in Research Archive Show summary

  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.

• Heggelund, Julie Elisabeth; Das, Saykat; Stamnæs, Jorunn; Iversen, Rasmus & Sollid, Ludvig Magne (2023). Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3. Nature Communications. 14:6216 (1), p. 1–11. doi: 10.1038/s41467-023-42004-z. Full text in Research Archive Show summary

  Abstract Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain and two C-terminal β-barrels (C1C2). Here, we report four X-ray crystal structures representing inactive and active conformations of human TG3 in complex with a TG3-specific Fab fragment of a DH patient derived antibody. We demonstrate that cleaved TG3, upon binding of a substrate-mimicking inhibitor, undergoes a large conformational change as a β-sheet in the catalytic core domain moves and C1C2 detaches. The unique enzyme-substrate conformation of TG3 without C1C2 is recognized by DH autoantibodies. The findings support a model where B-cell receptors of TG3-specific B cells bind and internalize TG3-gluten enzyme-substrate complexes thereby facilitating gluten-antigen presentation, T-cell help and autoantibody production.

• Das, Saykat; Stamnæs, Jorunn; Kemppainen, Esko; Hervonen, Kaisa; Lundin, Knut & Parmar, Naveen [Show all 12 contributors for this article] (2023). Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis. Advanced Science. 10:2300401(25), p. 1–10. doi: 10.1002/advs.202300401. Full text in Research Archive Show summary

  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.

• 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), p. 1–15. doi: 10.1371/journal.pone.0287662. Full text in Research Archive Show summary

  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.

• Amundsen, Sunniva Furre; Stamnæs, Jorunn; Pré, Marie Fleur du & Sollid, Ludvig Magne (2022). Transglutaminase 2 affinity and enzyme-substrate intermediate stability as determining factors for T-cell responses to gluten peptides in celiac disease. European Journal of Immunology. ISSN 0014-2980. 52(9), p. 1474–1481. doi: 10.1002/eji.202249862. Full text in Research Archive Show summary

  The adaptive immune response of celiac disease (CeD) involves presentation of gluten peptides to CD4+ T cells by transglutaminase 2 (TG2) specific B cells. This B-cell/T-cell crosstalk is facilitated by involvement of TG2:gluten peptide complexes that act principally in the form of enzyme-substrate intermediates. Here, we have addressed how gluten peptide affinity and complex stability in the presence of secondary substrates affect the uptake of TG2:gluten peptide complexes by TG2-specific B cells and the activation of gluten-specific T cells. We studied affinity of various gluten peptides for TG2 by biochemical assay, and monitored uptake of gluten peptides by TG2-specific B cells by flow cytometry. Crosstalk between TG2-specific B cells and gluten-specific T cells was assayed with transfectants expressing antigen receptors derived from CeD patients. We found that gluten peptides with high TG2 affinity showed better uptake by TG2-specific B cells. Uptake by B cells, and subsequent activation of T cells, was negatively affected by polyamines acting as secondary TG2 substrates. These results show that affinity between gluten peptide and TG2 governs the selection of T-cell epitopes via enhanced uptake of TG2:gluten complexes by TG2-specific B cells, and that exogenous polyamines can influence the CeD immune responses by disrupting TG2:gluten complexes.

• Lindstad, Christian Borgen; Pré, Marie Fleur du; Stamnæs, Jorunn & Sollid, Ludvig Magne (2022). Injection of prototypic celiac anti-transglutaminase 2 antibodies in mice does not cause enteropathy. PLOS ONE. 17:e0266543(4), p. 1–13. doi: 10.1371/journal.pone.0266543. Full text in Research Archive Show summary

  Background Celiac disease is an autoimmune enteropathy driven by dietary intake of gluten proteins. Typical histopathologic features are villous flattening, crypt hyperplasia and infiltration of inflammatory cells in the intestinal epithelium and lamina propria. The disease is hallmarked by the gluten-dependent production of autoantibodies targeting the enzyme transglutaminase 2 (TG2). While these antibodies are specific and sensitive diagnostic markers of the disease, a role in the development of the enteropathy has never been established. Methods We addressed this question by injecting murine antibodies harboring the variable domains of a prototypic celiac anti-TG2 immunoglobulin into TG2-sufficient and TG2-deficient mice evaluating for celiac enteropathy. Results We found no histopathologic abnormalities nor clinical signs of disease related to the injection of anti-TG2 IgG or IgA. Conclusions Our findings do not support a direct role for secreted anti-TG2 antibodies in the development of the celiac enteropathy.

• Stamnæs, Jorunn; Stray, Daniel; Stensland, Maria; Sarna, Vikas Kumar; Nyman, Tuula Anneli & Lundin, Knut Erik Aslaksen [Show all 7 contributors for this article] (2021). In well‐treated celiac patients low‐level mucosal inflammation predicts response to 14‐day gluten challenge. Advanced Science. 8:2003526(4), p. 1–7. doi: 10.1002/advs.202003526. Full text in Research Archive Show summary

  In celiac disease (CeD), gluten activates adaptive immune cells that cause damage to the small intestinal mucosa. Histological evaluation of intestinal biopsies allows for grading of disease severity. CeD can effectively be treated with a life-long gluten-free diet. Gluten challenge of treated CeD patients is used to confirm diagnosis and to test drug efficacy in clinical trials, but patients respond with different magnitudes to the same gluten challenge. In this study of 19 well-treated CeD patients, proteome analysis of total tissue or isolated epithelial cell compartment from formalin-fixed paraffin embedded biopsies collected before and after 14-day gluten challenge demonstrates that patients with strong mucosal response to challenge have signs of ongoing tissue inflammation already before challenge. This low-level tissue inflammation at baseline is paralleled by increased gluten specific CD4+ T-cell frequencies in the gut and presence of a low-level blood inflammatory profile. Thus, apparently well-treated CeD is frequently not entirely quiescent, with presence of low-grade inflammation and antigluten immunity in the gut mucosa. Histology assessment alone appears insufficient to judge full recovery and gut mucosal healing of CeD patients. The findings raise a concern whether a seemingly proper gluten-free diet is able to curb gut inflammation in all CeD patients.

• Stamnæs, Jorunn (2021). Insights from tissue “omics” analysis on intestinal remodeling in celiac disease. Proteomics. ISSN 1615-9853. 21:2100057(23-24), p. 1–13. doi: 10.1002/pmic.202100057. Full text in Research Archive Show summary

  Celiac disease (CeD) is a prevalent intestinal disorder that only develops in genetically susceptible individuals when they mount a harmful CD4+ T-cell response towards gluten peptides. Intake of gluten leads to inflammation and remodeling of the small intestine with symptoms such as nausea and diarrhea. The only current treatment is a lifelong gluten free diet. The immunological basis for CeD is well characterized but the mechanisms that drive intestinal remodeling are still poorly understood. Transcriptome or proteome analysis of intestinal biopsies gives a global snapshot of all processes that occur in the tissue, including alterations in the epithelial cell layer. This paper will introduce concepts of intestinal remodeling, recapitulate the current understanding of CeD pathogenesis and discuss findings from relevant tissue “omics” studies. On the basis of this review, I give perspectives on what tissue “omics” studies can tell us about disease pathogenesis with a particular focus on the gluten induced intestinal remodeling.

• Lindstad, Christian Borgen; Dewan, Alisa Elinsdatter; Stamnæs, Jorunn; Sollid, Ludvig Magne & Pré, Marie Fleur du (2021). TG2-gluten complexes as antigens for gluten-specific and transglutaminase-2 specific B cells in celiac disease. PLOS ONE. 16:e0259082(11), p. 1–14. doi: 10.1371/journal.pone.0259082. Full text in Research Archive Show summary

  A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4 + T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4 + T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones. We show that multivalent TG2-gluten complexes are efficient antigens for both TG2-specific and DGP-specific B cells and allow both types of B cells to receive help from gluten-specific T cells of many different specificities.

• Pré, Fleur du; Blazevski, Jana; Dewan, Alisa Elinsdatter; Stamnæs, Jorunn; Kanduri, Srinivasa Kalyana Chakravarthi & Sandve, Geir Kjetil [Show all 13 contributors for this article] (2020). B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2. Journal of Experimental Medicine (JEM). ISSN 0022-1007. 217:e20190860.(2), p. 1–14. doi: 10.1084/jem.20190860. Full text in Research Archive Show summary

  Autoantibodies to transglutaminase 2 (TG2) are hallmarks of celiac disease. To address B cell tolerance and autoantibody formation to TG2, we generated immunoglobulin knock-in (Ig KI) mice that express a prototypical celiac patient–derived anti-TG2 B cell receptor equally reactive to human and mouse TG2. We studied B cell development in the presence/absence of autoantigen by crossing the Ig KI mice to Tgm2−/− mice. Autoreactive B cells in Tgm2+/+ mice were indistinguishable from their naive counterparts in Tgm2−/− mice with no signs of clonal deletion, receptor editing, or B cell anergy. The autoreactive B cells appeared ignorant to their antigen, and they produced autoantibodies when provided T cell help. The findings lend credence to a model of celiac disease where gluten-reactive T cells provide help to autoreactive TG2-specific B cells by involvement of gluten–TG2 complexes, and they outline a general mechanism of autoimmunity with autoantibodies being produced by ignorant B cells on provision of T cell help.

• Iversen, Rasmus; Amundsen, Sunniva Furre; Kleppa, Liv; Pré, Marie Fleur du; Stamnæs, Jorunn & Sollid, Ludvig Magne (2020). Evidence that pathogenic transglutaminase 2 in celiac disease derives from enterocytes. Gastroenterology. ISSN 0016-5085. 159(2), p. 788–790. doi: 10.1053/j.gastro.2020.04.018. Full text in Research Archive
• Iversen, Rasmus; Roy, Bishnudeo; Stamnæs, Jorunn; Høydahl, Lene Støkken; Hnida, Kathrin & Neumann, Ralf Stefan [Show all 9 contributors for this article] (2019). Efficient T cell–B cell collaboration guides autoantibody epitope bias and onset of celiac disease. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 116(30), p. 15134–15139. doi: 10.1073/pnas.1901561116. Full text in Research Archive Show summary

  B cells play important roles in autoimmune diseases through autoantibody production, cytokine secretion, or antigen presentation to T cells. In most cases, the contribution of B cells as antigen-presenting cells is not well understood. We have studied the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease patients by generating recombinant antibodies from single gut plasma cells reactive with discrete antigen domains and by undertaking proteomic analysis of anti-TG2 serum antibodies. The majority of the cells recognized epitopes in the N-terminal domain of TG2. Antibodies recognizing C-terminal epitopes interfered with TG2 cross-linking activity, and B cells specific for C-terminal epitopes were inefficient at taking up TG2-gluten complexes for presentation to gluten-specific T cells. The bias toward N-terminal epitopes hence reflects efficient T-B collaboration. Production of antibodies against N-terminal epitopes coincided with clinical onset of disease, suggesting that TG2-reactive B cells with certain epitope specificities could be the main antigen-presenting cells for pathogenic, gluten-specific T cells. The link between B cell epitopes, antigen presentation, and disease onset provides insight into the pathogenic mechanisms of a T cell-mediated autoimmune condition.

• Tutturen, Astrid Elisabeth Voorham; Dørum, Siri; Clancy, Trevor; Reims, Henrik Mikael; Christophersen, Asbjørn & Lundin, Knut Erik Aslaksen [Show all 9 contributors for this article] (2018). Characterization of the Small Intestinal Lesion in Celiac Disease by Label-Free Quantitative Mass Spectrometry. American Journal of Pathology. ISSN 0002-9440. 188(7), p. 1563–1579. doi: 10.1016/j.ajpath.2018.03.017. Full text in Research Archive Show summary

  Global characterization of tissue proteomes from small amounts of biopsy material has become feasible because of advances in mass spectrometry and bioinformatics tools. In celiac disease (CD), dietary gluten induces an immune response that is accompanied by pronounced remodeling of the small intestine. Removal of gluten from the diet abrogates the immune response, and the tissue architecture normalizes. In this study, differences in global protein expression of small intestinal biopsy specimens from CD patients were quantified by analyzing formalin-fixed, paraffin-embedded material using liquid chromatography–mass spectrometry and label-free protein quantitation. Protein expression was compared in biopsy specimens collected from the same patients before and after 1-year treatment with gluten-free diet (n = 10) or before and after 3-day gluten provocation (n = 4). Differential expression of proteins in particular from mature enterocytes, neutrophils, and plasma cells could distinguish untreated from treated CD mucosa, and Ig variable region IGHV5-51 expression was found to serve as a CD-specific marker of ongoing immune activation. In patients who had undergone gluten challenge, coordinated up-regulation of wound response proteins, including the CD autoantigen transglutaminase 2, was observed. Our study provides a global and unbiased assessment of antigen-driven changes in protein expression in the celiac intestinal mucosa.

• Cardoso, Ines Do Rosario; Østerlund, Eva Christina; Stamnæs, Jorunn; Iversen, Rasmus; Andersen, Jan Terje & Jørgensen, Thomas J D [Show all 7 contributors for this article] (2017). Dissecting the interaction between transglutaminase 2 and fibronectin. Amino Acids. ISSN 0939-4451. 49(3), p. 489–500. doi: 10.1007/s00726-016-2296-y. Full text in Research Archive Show summary

  In the extracellular environment, the enzyme transglutaminase 2 (TG2) is involved in cell–matrix interactions through association with the extracellular matrix protein, fibronectin (FN). The 45 kDa gelatin-binding domain of FN (45FN) is responsible for the binding to TG2. Previous studies have demonstrated that the FN-binding site of TG2 is located in the N-terminal domain of the enzyme although with conflicting results regarding the specific residues involved. Here we have mapped the FN interaction site of human TG2 by use of hydrogen/deuterium exchange coupled with mass spectrometry, and we confirm that the FN-binding site is located in the N-terminal domain of TG2. Furthermore, by combination of site-directed mutagenesis and surface plasmon resonance analysis we have identified the TG2 residues K30, R116 and H134 as crucial to maintain the high affinity interaction with FN. Mutation of all three residues simultaneously reduced binding to 45FN by more than 2000-fold. We also identified residues in the catalytic core domain of TG2 that contributed to FN binding, hence extending the binding interface between TG2 and FN. This study provides new insights into the high affinity interaction between TG2 and FN. This is a post-peer-review, pre-copyedit version of an article published in Amino Acids. The final authenticated version is available online.

• Stamnæs, Jorunn; Cardoso, Ines Do Rosario; Iversen, Rasmus & Sollid, Ludvig Magne (2016). Transglutaminase 2 strongly binds to an extracellular matrix component other than fibronectin via its second C-terminal beta-barrel domain. The FEBS Journal. ISSN 1742-464X. 283(21), p. 3994–4010. doi: 10.1111/febs.13907. Full text in Research Archive

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• Risum, Kristine; Stamnæs, Jorunn; Alexanderson, Helene; Molberg, Øyvind & Sanner, Helga (2026). Altered acute inflammatory response to maximal treadmill exercise in children and adolescents with juvenile idiopathic arthritis. Full text in Research Archive

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