Andreas Lossius

• Torkildsen, Øivind; Brustad, Hilde Kjelgaard; Høgestøl, Einar August; Alstadhaug, Karl Bjørnar; Bhan, Alok & Flemmen, Heidi Øyen [Vis alle 22 forfattere av denne artikkelen] (2026). Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis. New England Journal of Medicine. ISSN 0028-4793. 395(1), s. 44–53. doi: 10.1056/nejmoa2600993. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking. METHODS In this phase 3, multicenter, double-blind, noninferiority trial, we randomly assigned adults with newly diagnosed relapsing multiple sclerosis and recent disease activity in a 3:2 ratio to receive rituximab or ocrelizumab every 6 months for 24 months. The primary end point was the absence of new or enlarging lesions on T2-weighted magnetic resonance imaging (MRI) from month 6 to month 24. Noninferiority was defined as a lower limit of the 95% confidence interval for the risk difference (ritux- imab minus ocrelizumab) of greater than or equal to −10 percentage points. Secondary end points included efficacy and safety. RESULTS A total of 218 participants underwent randomization; 216 received treatment (132 assigned to the rituximab group and 84 assigned to the ocrelizumab group). Between months 6 and 24, the estimated probability of having no new or enlarging lesions detected on T2-weighted MRI was 92.2% with rituximab and 94.8% with ocrelizumab, corresponding to a risk difference of –2.6 percentage points (95% confidence interval, –9.4 to 4.3), which met the prespecified noninferiority criterion. Relapse rates, dis- ability outcomes, and cognitive-performance profiles appeared to be similar in the two groups. Infections were more common in the rituximab group than in the ocreliz- umab group (in 82% vs. 69% of participants), although the percentage of participants with serious adverse events was similar in the two groups (8% and 7%, respectively). CONCLUSIONS In participants with newly diagnosed relapsing multiple sclerosis and recent disease activity, rituximab was noninferior to ocrelizumab in suppressing disease activity as detected by MRI from 6 to 24 months, with a similar incidence of serious adverse events.

• Seyedraoufi, Seyedmojtaba; Gornitzka, Mari Bergstøl & Lossius, Andreas (2026). GATHeR: graph-based accurate tool for immunoglobulin heavy- and light-chain reconstruction. Nature Communications. doi: 10.1038/s41467-026-74272-w. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Recovering full-length, paired B-cell receptor (BCR) sequences from scRNA-seq reads remains difficult, especially in naive and memory B cells where immunoglobulin transcripts are sparse. Incomplete constant-region coverage in current methods limits isoform, subclass, and allele resolution. Here we present GATHeR, an open-source tool that assembles and annotates paired heavy- and light-chain BCR sequences and extends assembled sequences into constant regions. This enables confident subclass and allele assignment and recovery of membrane-bound isoforms, including the transmembrane segment and cytoplasmic tail, thereby distinguishing surface BCRs from secreted antibodies. GATHeR supports Smart-seq2/3 and 10x Genomics libraries and outperforms existing methods across benchmarks, with the largest gains in naive and memory B cells. Notably, in these populations the constant-region extension also enables detection of splice variation, including intron-containing heavy-chain transcripts with read-level support. By delivering high-fidelity receptor, isoform, and clonal lineage information, GATHeR broadens the analytical reach of scRNA-seq for B-cell immunology.

• Gornitzka, Mari B.; Røsjø, Egil Rørvik; Jana, Uddalok; Ford, Easton E.; Tourancheau, Alan & Lees, William D. [Vis alle 10 forfattere av denne artikkelen] (2025). Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy-chain locus. Genome Research. ISSN 1088-9051. 35(10), s. 2240–2251. doi: 10.1101/gr.280400.125. Fulltekst i vitenarkiv Vis sammendrag

  Genetic diversity within the human immunoglobulin heavy-chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method that combines Oxford Nanopore Technologies ultra-long sequencing and adaptive sampling with a bioinformatic pipeline to produce haplotype-resolved, annotated IGH assemblies. Notably, our strategy overcomes prior limitations in phasing resolution, enabling single-contig haplotype assemblies that span the entire IGH locus. We apply this method to four individuals and validate the accuracy of the IGH assemblies using Pacific Biosciences HiFi reads, demonstrating near-complete sequence congruence, with only some residual indel errors. Moreover, when applied to the reference material HG002, our pipeline reveals no base differences and a limited number of indels compared with the telomere-to-telomere genome benchmark across the IGH region. Importantly, in the four individuals, our approach uncovers 28 novel alleles and previously uncharacterized large structural variants, including a 120 kb duplication spanning IGHE to IGHA1 within the IGH constant region (IGHC) and, within the IGHV region, an expanded seven-copy IGHV3-23 gene haplotype. These findings underscore the power of our method to resolve the full complexity of the IGH locus and uncover previously unrecognized variants that may affect immune function and disease susceptibility. Thus, our method provides a strong basis for future immunological research and translational applications.

• Polak, Justyna; Wagnerberger, Johanna Henny; Torsetnes, Silje Bøen; Lindeman, Ida; Høglund, Rune Alexander Aamodt & Vartdal, Frode [Vis alle 8 forfattere av denne artikkelen] (2023). Single-cell transcriptomics combined with proteomics of intrathecal IgG reveal transcriptional heterogeneity of oligoclonal IgG-secreting cells in multiple sclerosis. Frontiers in Cellular Neuroscience. 17. doi: 10.3389/fncel.2023.1189709. Fulltekst i vitenarkiv Vis sammendrag

  The phenotypes of B lineage cells that produce oligoclonal IgG in multiple sclerosis have not been unequivocally determined. Here, we utilized single-cell RNA-seq data of intrathecal B lineage cells in combination with mass spectrometry of intrathecally synthesized IgG to identify its cellular source. We found that the intrathecally produced IgG matched a larger fraction of clonally expanded antibody-secreting cells compared to singletons. The IgG was traced back to two clonally related clusters of antibody-secreting cells, one comprising highly proliferating cells, and the other consisting of more differentiated cells expressing genes associated with immunoglobulin synthesis. These findings suggest some degree of heterogeneity among cells that produce oligoclonal IgG in multiple sclerosis.

• Lindeman, Ida; Polak, Justyna; Qiao, Shuo-Wang; Holmøy, Trygve; Høglund, Rune Alexander & Vartdal, Frode [Vis alle 9 forfattere av denne artikkelen] (2022). Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis. European Journal of Immunology. ISSN 0014-2980. 52(4), s. 550–565. doi: 10.1002/eji.202149576. Fulltekst i vitenarkiv Vis sammendrag

  Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of MS patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and BCR reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell (ASC) compartments and observed clonally related cells of different isotypes including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in ASCs, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy-chain variable (IGHV)4 gene family with the κ variable (IGKV)1 gene family. The IGHV4-39 gene was most used and showed the highest frequency of pairing with IGKV1-5 and IGKV1(D)-33. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS and indicate that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes

• Amoriello, Roberta; Chernigovskaia, Mariia; Greiff, Victor; Carnasciali, Alberto; Massacesi, Luca & Barilaro, Alessandro [Vis alle 13 forfattere av denne artikkelen] (2021). TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood. EBioMedicine. 68:103429, s. 1–13. doi: 10.1016/j.ebiom.2021.103429. Fulltekst i vitenarkiv Vis sammendrag

  Background T cells play a key role in the pathogenesis of multiple sclerosis (MS), a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although several studies recently investigated the T-cell receptor (TCR) repertoire in cerebrospinal fluid (CSF) of MS patients by high-throughput sequencing (HTS), a deep analysis on repertoire similarities and differences among compartments is still missing. Methods We performed comprehensive bioinformatics on high-dimensional TCR Vβ sequencing data from published and unpublished MS and healthy donors (HD) studies. We evaluated repertoire polarization, clone distribution, shared CDR3 amino acid sequences (CDR3s-a.a.) across repertoires, clone overlap with public databases, and TCR similarity architecture. Findings CSF repertoires showed a significantly higher public clones percentage and sequence similarity compared to peripheral blood (PB). On the other hand, we failed to reject the null hypothesis that the repertoire polarization is the same between CSF and PB. One Primary-Progressive MS (PPMS) CSF repertoire differed from the others in terms of TCR similarity architecture. Cluster analysis splits MS from HD. Interpretation In MS patients, the presence of a physiological barrier, the blood-brain barrier, does not impact clone prevalence and distribution, but impacts public clones, indicating CSF as a more private site. We reported a high Vβ sequence similarity in the CSF-TCR architecture in one PPMS. If confirmed it may be an interesting insight into MS progressive inflammatory mechanisms. The clustering of MS repertoires from HD suggests that disease shapes the TCR Vβ clonal profile. Funding This study was partly financially supported by the Italian Multiple Sclerosis Foundation (FISM), that contributed to Ballerini-DB data collection (grant #2015 R02).

• Høglund, Rune Alexander; Bremel, Robert; Homan, E. Jane; Torsetnes, Silje Bøen; Lossius, Andreas & Holmøy, Trygve (2020). CD4+ T Cells in the Blood of MS Patients Respond to Predicted Epitopes From B cell Receptors Found in Spinal Fluid. Frontiers in Immunology. 11, s. 1–12. doi: 10.3389/fimmu.2020.00598. Fulltekst i vitenarkiv Vis sammendrag

  B cells are important pathogenic players in multiple sclerosis (MS), but their exact role is not known. We have previously demonstrated that B cells from cerebrospinal fluid (CSF) of MS patients can activate T cells that specifically recognize antigenic determinants (idiotopes) from their B cell receptors (BCRs). The aim of this study was to evaluate whether in silico prediction models could identify antigenic idiotopes of immunoglobulin heavy-chain variable (IGHV) transcriptomes in MS patients. We utilized a previously assembled dataset of CSF IGHV repertoires from MS patients. To guide selection of potential antigenic idiotopes, we used in silico predicted HLA-DR affinity, endosomal processing, as well as transcript frequency from nine MS patients. Idiotopes with predicted low affinity and low likelihood of cathepsins cleavage were inert controls. Peripheral blood mononuclear cells from these patients were stimulated with the selected idiotope peptides in presence of anti-CD40 for 12 h. T cells were then labeled for activation status with anti-CD154 antibodies and CD3+CD4+ T cells phenotyped as memory (CD45RO+) or naïve (CD45RO−), with potential for brain migration (CXCR3 and/or CCR6 expression). Anti-CD14 and -CD8 were utilized to exclude monocytes and CD8+ T cells. Unstimulated cells or insulin peptides were negative controls, and EBNA-1 peptides or CD3/CD28 beads were positive controls. The mean proportion of responding memory CD4+ T cells from all nine MS patients was significantly higher for idiotope peptides with predicted high HLA-DR affinity and high likelihood of cathepsin cleavage, than toward predicted inert peptides. Responses were mainly observed toward peptides affiliated with the CDR3 region. Activated memory CD4+ T cells expressed the chemokine receptor CCR6, affiliated with a Th17 phenotype and allowing passage into the central nervous system (CNS). This in vitro study suggests that that antigenic properties of BCR idiotopes can be identified in silico using HLA affinity and endosomal processing predictions. It further indicates that MS patients have a memory T cell repertoire capable of recognizing frequent BCR idiotopes found in endogenous CSF, and that these T cells express chemokine receptors allowing them to reach the CSF B cells expressing these idiotopes.

• Høglund, Rune Alexander; Torsetnes, Silje Bøen; Lossius, Peter Andreas Vold; Bogen, Bjarne; Homan, E. Jane & Bremel, Robert [Vis alle 7 forfattere av denne artikkelen] (2019). Human cysteine cathepsins degrade immunoglobulin G in vitro in a predictable manner. International Journal of Molecular Sciences. ISSN 1661-6596. 20:4843(19), s. 1–19. doi: 10.3390/ijms20194843. Fulltekst i vitenarkiv Vis sammendrag

  Cysteine cathepsins are critical components of the adaptive immune system involved in the generation of epitopes for presentation on human leukocyte antigen (HLA) molecules and have been implicated in degradation of autoantigens. Immunoglobulin variable regions with somatic mutations and random complementarity region 3 amino acid composition are inherently immunogenic. T cell reactivity towards immunoglobulin variable regions has been investigated in relation to specific diseases, as well as reactivity to therapeutic monoclonal antibodies. Yet, how the immunoglobulins, or the B cell receptors, are processed in endolysosomal compartments of professional antigen presenting cells has not been described in detail. Here we present in silico and in vitro experimental evidence suggesting that cysteine cathepsins S, L and B may have important roles in generating peptides fitting HLA class II molecules, capable of being presented to T cells, from monoclonal antibodies as well as from central nervous system proteins including a well described autoantigen. By combining neural net models with in vitro proteomics experiments, we further suggest how such degradation can be predicted, how it fits with available cellular models, and that it is immunoglobulin heavy chain variable family dependent. These findings are relevant for biotherapeutic drug design as well as to understand disease development. We also suggest how these tools can be improved, including improved machine learning methodology.

• Myhr, Kjell-Morten; Torkildsen, Øivind; Lossius, Peter Andreas Vold; Bø, Lars & Holmøy, Trygve (2019). B cell depletion in the treatment of multiple sclerosis. Expert Opinion on Biological Therapy. ISSN 1471-2598. 19(3), s. 261–271. doi: 10.1080/14712598.2019.1568407. Fulltekst i vitenarkiv
• Tomescu-Baciu, Alina; Johansen, Jorunn; Holmøy, Trygve; Greiff, Victor; Stensland, Maria & Souza, Gustavo Antonio De [Vis alle 8 forfattere av denne artikkelen] (2019). Persistence of intrathecal oligoclonal B cells and IgG in multiple sclerosis. Journal of Neuroimmunology. ISSN 0165-5728. 333:576966, s. 1–7. doi: 10.1016/j.jneuroim.2019.576966. Fulltekst i vitenarkiv Vis sammendrag

  In multiple sclerosis (MS), B cells are trafficking across the blood-brain barrier, but it is not known how this relates to the synthesis of oligoclonal IgG. We used quantitative mass spectrometry of oligoclonal bands and high-throughput sequencing of immunoglobulin heavy-chain variable transcripts to study the longitudinal B cell response in the cerebrospinal fluid (CSF) and blood of two MS patients. Twenty of 22 (91%) and 25 of 28 (89%) of oligoclonal band peptides persisted in samples collected 18 months apart, in spite of a dynamic exchange across the blood-CSF barrier of B lineage cells connecting to oligoclonal IgG.

• Høglund, Rune Alexander; Polak, Justyna; Vartdal, Frode; Holmøy, Trygve & Lossius, Peter Andreas Vold (2018). B-cell composition in the blood and cerebrospinal fluid of multiple sclerosis patients treated with dimethyl fumarate. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 26, s. 90–95. doi: 10.1016/j.msard.2018.08.032. Fulltekst i vitenarkiv Vis sammendrag

  Background:B cells may contribute to the immunopathogenesis of multiple sclerosis (MS). Dimethyl fumarate(DMF) has recently been shown to reduce the frequency of memory B cells in blood, but it is not known whetherthe drug influences the cellular composition in the cerebrospinalfluid (CSF).Methods:A cross-sectional study examining the cellular composition in blood and cerebrospinalfluid (CSF) from10 patients treated with DMF and 18 patients receiving other disease modifying drugs or no treatment.Results:Patients treated with DMF had reduced proportions of memory B cells in blood compared to other MSpatients (p=0.0007), and the reduction correlated with treatment duration (rs=−0.75,p=0.021). In theCSF, the absolute number of mononuclear cells were significantly lower in DMF-treated patients compared to theother patients (p= 0.023), and there was a disproportionate decrease of plasmablasts (p=0.031).Conclusion:The results of this exploratory study support a B-cell mediated mechanism of action for DMF in bothblood and CSF.

• Tomescu-Baciu, Alina; Vartdal, Frode; Holmøy, Trygve; Vedeler, Christian A. & Lossius, Peter Andreas Vold (2018). G1m1 predominance of intrathecal virus-specific antibodies in multiple sclerosis. Annals of clinical and translational neurology. 5(10), s. 1303–1309. doi: 10.1002/acn3.642. Fulltekst i vitenarkiv Vis sammendrag

  We have previously shown that plasmablasts of the G1m1 allotype of IgG1 are selectively enriched in the cerebrospinal fluid of G1m1/G1m3 heterozygous patients with multiple sclerosis, whereas both allotypes are equally used in neuroborreliosis. Here, we demonstrate a strong preference for the G1m1 allotype in the intrathecal humoral immune responses against measles, rubella, and varicella zoster virus in G1m1/G1m3 heterozygous multiple sclerosis patients. Conversely, intrathecally synthesized varicella zoster virus‐specific IgG1 in varicella zoster virus meningoencephalitis comprised both allotypes. This implies that G1m1 B cells are selected to the central nervous system of multiple sclerosis patients regardless of specificity and suggests that an antigen‐independent mechanism could drive the intrathecal humoral immune response.

• Høglund, Rune Alexander; Lossius, Peter Andreas Vold; Johansen, Jorunn; Homan, Jane; Benth, Jurate Saltyte & Robins, Harlan [Vis alle 9 forfattere av denne artikkelen] (2017). In silico prediction analysis of idiotope-driven T-B cell collaboration in multiple sclerosis. Frontiers in Immunology. 8. doi: 10.3389/fimmu.2017.01255. Fulltekst i vitenarkiv Vis sammendrag

  Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS), but the antigen they present remains unknown. We hypothesized that B cells may activate CD4+ T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA) class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients and 6 controls with other inflammatory neurological disorders (OINDs), to assess whether the prerequisites for such idiotope-driven T–B cell collaboration are present. Our findings indicate that idiotopes from the complementarity determining region (CDR) 3 of MS patients on average have high predicted affinities for disease associated HLA-DRB1*15:01 molecules and are predicted to be endosomally processed by cathepsin S and L in positions that allows such HLA binding to occur. Additionally, complementarity determining region 3 sequences from cerebrospinal fluid (CSF) B cells from MS patients contain on average more rare T cell-exposed motifs that could potentially escape tolerance and stimulate CD4+ T cells than CSF B cells from OIND patients. Many of these features were associated with preferential use of the IGHV4 gene family by CSF B cells from MS patients. This is the first study to combine high-throughput sequencing of patient immune repertoires with large-scale prediction analysis and provides key indicators for future in vitro and in vivo analyses.

• Røsjø, Egil Rørvik; Lossius, Peter Andreas Vold; Abdelmagid, Nada; Lindstrøm, Jonas Christoffer; Kampman, Margitta Theodora & Jørgensen, Lone [Vis alle 11 forfattere av denne artikkelen] (2017). Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis. Multiple Sclerosis. ISSN 1352-4585. 23(3), s. 395–402. doi: 10.1177/1352458516654310. Fulltekst i vitenarkiv
• Lossius, Peter Andreas Vold; Tomescu-Baciu, Alina; Holmøy, Trygve; Vedeler, Christian A.; Røsjø, Egil Rørvik & Lorentzen, Åslaug Rudjord [Vis alle 8 forfattere av denne artikkelen] (2017). Selective intrathecal enrichment of G1m1-positive B cells in multiple sclerosis. Annals of clinical and translational neurology. 4(10), s. 756–761. doi: 10.1002/acn3.451. Fulltekst i vitenarkiv Vis sammendrag

  Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF). However, how these variants are implicated in disease mechanisms remains unknown. Here, we show that proliferating plasmablasts expressing the G1m1 allotype of IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients, whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme neuroborreliosis displayed oligoclonal IgG1 of both allotypes. This points to a disease‐specific mechanism involved in B‐cell establishment within the central nervous system in MS.

• Lossius, Peter Andreas Vold; Johansen, Jorunn; Vartdal, Frode & Holmøy, Trygve (2016). High-throughput sequencing of immune repertoires in multiple sclerosis. Annals of clinical and translational neurology. 3(4), s. 295–306. doi: 10.1002/acn3.295. Fulltekst i vitenarkiv Vis sammendrag

  T cells and B cells are crucial in the initiation and maintenance of multiple sclerosis (MS), and the activation of these cells is believed to be mediated through specific recognition of antigens by the T- and B-cell receptors. The antigen receptors are highly polymorphic due to recombination (T- and B-cell receptors) and mutation (B-cell receptors) of the encoding genes, which can therefore be used as fingerprints to track individual T- and B-cell clones. Such studies can shed light on mechanisms driving the immune responses and provide new insights into the pathogenesis. Here, we summarize studies that have explored the T- and B-cell receptor repertoires using earlier methodological approaches, and we focus on how high-throughput sequencing has provided new knowledge by surveying the immune repertoires in MS in even greater detail and with unprecedented depth.

• Johansen, Jorunn; Vartdal, Frode; Desmarais, Cindy; Tutturen, Astrid Elisabeth Voorham; Souza, Gustavo Antonio De & Lossius, Peter Andreas Vold [Vis alle 7 forfattere av denne artikkelen] (2015). Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome. Clinical Immunology. ISSN 1521-6616. 160(2), s. 211–225. doi: 10.1016/j.clim.2015.06.001. Fulltekst i vitenarkiv
• Løken-Amsrud, Kristin Ingeleiv; Lossius, Peter Andreas Vold; Torkildsen, Øivind & Holmøy, Trygve (2015). Miljøets betydning ved multippel sklerose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 135(9), s. 856–860. doi: 10.4045/tidsskr.14.0751. Fulltekst i vitenarkiv
• Wesnes, Kristin; Riise, Trond; Casetta, Ilaria; Drulovic, Jelena; Granieri, Enrico & Holmøy, Trygve [Vis alle 16 forfattere av denne artikkelen] (2015). Body size and the risk of multiple sclerosis in Norway and Italy: The EnvIMS study. Multiple Sclerosis. ISSN 1352-4585. 21(4), s. 388–395. doi: 10.1177/1352458514546785. Fulltekst i vitenarkiv
• Lossius, Peter Andreas Vold; Johansen, Jorunn; Vartdal, Frode; Robins, Harlan; Benth, Jurate Saltyte & Holmøy, Trygve [Vis alle 7 forfattere av denne artikkelen] (2014). High-throughput sequencing of TCR repertoires in multiple sclerosis reveals intrathecal enrichment of EBV-reactive CD8+ T cells. European Journal of Immunology. ISSN 0014-2980. 44(11), s. 3439–3452. doi: 10.1002/eji.201444662. Fulltekst i vitenarkiv
• Lossius, Peter Andreas Vold; Riise, Trond; Pugliatti, Maura; Bjørnevik, Kjetil Lauvland; Casetta, Ilaria & Drulovic, Jelena [Vis alle 16 forfattere av denne artikkelen] (2014). Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study. Multiple Sclerosis. ISSN 1352-4585. 20(6), s. 669–674. doi: 10.1177/1352458513505693. Fulltekst i vitenarkiv
• Bjørnevik, Kjetil Lauvland; Riise, Trond; Casetta, Ilaria; Drulovic, Jelena; Granieri, Enrico & Holmøy, Trygve [Vis alle 16 forfattere av denne artikkelen] (2014). Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study. Multiple Sclerosis. ISSN 1352-4585. 20(8), s. 1042–1049. doi: 10.1177/1352458513513968. Fulltekst i vitenarkiv
• Vold, Lossius Peter Andreas; Johansen, Jorunn; Torkildsen, Øivind; Vartdal, Frode & Holmøy, Trygve (2012). Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses. 4(12), s. 3701–3730. doi: 10.3390/v4123701. Fulltekst i vitenarkiv
• Holmøy, Trygve; Lossius, Peter Andreas Vold; Gundersen, Thomas Erik; Moen, Stine Marit; Castellazzi, Massimilano & Fainardi, Enrico [Vis alle 7 forfattere av denne artikkelen] (2012). Intrathecal levels of vitamin D and IgG in multiple sclerosis. Acta Neurologica Scandinavica. ISSN 0001-6314. 125(6), s. e28–e31. doi: 10.1111/j.1600-0404.2011.01577.x. Fulltekst i vitenarkiv
• Lossius, Peter Andreas Vold; Vartdal, Frode & Holmøy, Trygve (2011). Vitamin D sensitive EBNA-1 specific T cells in the cerebrospinal fluid of patients with multiple sclerosis. Journal of Neuroimmunology. ISSN 0165-5728. 240, s. 87–96. doi: 10.1016/j.jneuroim.2011.09.011. Fulltekst i vitenarkiv

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• Gilmour, Brian Christopher; Visser, Johan Georg; Köhn-Luque, Alvaro; Lossius, Andreas & Spurkland, Anne (2024). SH2D2A Is an Indicator of Favourable Prognosis in Bladder Cancer and Is Enriched in Activated Treg Cells. Fulltekst i vitenarkiv
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Phuyal, Santosh; Lossius, Andreas & Spurkland, Anne (2023). β2, or not β2? Connecting the Lck-adaptor TSAd to integrin β2 via a combined wet lab & bioinformatic approach. Fulltekst i vitenarkiv
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Georg, Visser Johan; Lossius, Andreas & Spurkland, Anne (2022). Applying bioinformatics to pick-apart elusive protein functions: Focusing on TSAd/SH2D2A, an immune kinase adaptor. Fulltekst i vitenarkiv
• Gornitzka, Mari Bergstøl; Lossius, Andreas; Røsjø, Egil Rørvik & Vartdal, Frode (2026). Resolving the Immunoglobulin Heavy Chain Locus Methodological advances, genetic diversity, and constant region bias in multiple sclerosis. Universitetet i Oslo. ISSN 9788234808791. Fulltekst i vitenarkiv Vis sammendrag

  Antibodies and B-cell receptors are central components of the human adaptive immune system. These molecules, collectively termed immunoglobulins, can bind a wide range of pathogens with remarkable specificity. This breadth of recognition is achieved through somatic recombination and hypermutation of the loci that encode immunoglobulins. The immunoglobulin heavy chain (IGH) locus encodes the largest subunit of this molecule, which forms the central scaffold, contributes to antigen binding, and mediates effector functions. The IGH locus is genetically complex due to extensive repetitive sequences, segmental duplications, and structural variation, which has limited comprehensive characterization; to date, the locus has been fully resolved only twice. The IGH locus displays considerable genetic variation between individuals, yet much of this diversity is still unmapped. Because germline IGH variation shapes the expressed antibody repertoire and influences immune responses to infection and vaccination, gaps in our understanding of IGH diversity impede efforts to study these germline effects. Closing this gap is therefore essential for advancing immunogenetics. A novel method for characterizing the IGH locus is presented in this thesis. We demonstrate that this method generates single-contig complete haplotypes with very few errors and employ it to 16 donors, completely resolving 31 new IGH haplotypes. Across these assemblies, we identify novel alleles, copy number variations and structural variants, which are likely to have biologically meaningful effects. The motivation for IGH locus characterization was to investigate haplotypes carrying different IGH constant gene polymorphisms. In particular, the G1m1 allotype of IgG1, which has a heavily biased expression pattern in multiple sclerosis. Using our method on a cohort of Norwegian patients, we mapped the genetic architecture of their IGH to reveal differences between G1m1 and non-G1m1-containing haplotypes. In the second part of this thesis, the emphasis turns from IGH germline genetics to expression of IGH transcripts. Immunoglobulin repertoires are frequently analyzed in the context of vaccination, infection, and autoimmunity, where selective usage of specific variable genes can shape functional outcomes. However, analyses of IGH constant-gene usage typically stop at the isotype level, overlooking the potential relevance of allelic variation in constant regions. To address this gap, we developed a tool for reconstructing and analyzing immunoglobulin sequences from single-cell RNA-seq data. This enables robust recovery of full-length paired heavy and light chains, even from cells with low transcript abundance. Overall, this thesis broadens our understanding of IGH genetic diversity and introduces two methodological approaches that make it possible to study immunogenetic variation with far greater resolution. These tools lay the groundwork for future efforts to link germline architecture with the behavior of expressed antibody repertoires.

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