{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:33:52Z","timestamp":1793658832953,"version":"4.5.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The B cell repertoire contains the recombined sequences that encode the entire antibody repertoire of an individual. The repertoire is made from three antigenic binding chains, namely the immunoglobulin heavy chain (IGH) and two immunoglobulin light chains, \u03ba (IGK) and \u03bb (IGL). Compared to the T cell repertoire, the B cell repertoire is understudied in inflammatory bowel diseases (IBD) even though different antibodies such as ASCA (Anti-Saccharomyces cerevisiae) and ANCA (Anti-Neutrophil Cytoplasmic Antibodies) have been shown to be elevated in individuals with IBD. To address this limitation, we profiled the B cell repertoire of peripheral blood from 27 treatment-naive individuals with CD and 21 age-matched symptomatic controls using bulk B cell receptor sequencing. The repertoire of individuals with CD showed a reduction in diversity and an increase in clonality. Furthermore, we observed a significant reduction in the expansion of IgM and IgD and an expansion of IgA2, and IgG2 clonotypes in individuals with CD relative to controls, suggesting an antigen-driven expansion. This was also supported by higher levels of somatic hypermutations, particularly in the complementary determining region 2 (CDR2) of immunoglobulin heavy chain, in individuals with CD relative to the control group. Thus, despite the small sample size, we identified multiple alterations in the B cell repertoire of individuals with CD, highlighting the potential of the B cell repertoire in identifying antigenic exposures implicated in the disease, demanding now larger international studies, ideally including also treatment-naive and pre-clinical cases.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1725813","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:55:36Z","timestamp":1770360936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["High throughput profiling of the B cell repertoire identifies systematic changes in the repertoire of individuals with Crohn\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Aya K. H.","family":"Mahdy","sequence":"first","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Taheri","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein","place":["Kiel, Germany"]},{"name":"Department of Biology and Biotechnology, University of Pavia","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte Lie","family":"H\u00f8ivik","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Oslo University Hospital","place":["Oslo, Norway"]},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"ElAbd","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Kiel University and University Hospital Schleswig-Holstein","place":["Kiel, Germany"]},{"name":"Institute for Digestive Research, Lithuanian University of Health Sciences","place":["Kaunas, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1954","article-title":"A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1","volume":"39","author":"Hampe","year":"2007","journal-title":"Nat Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e39982","DOI":"10.7554\/eLife.39982","article-title":"The Crohn\u2019s disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1\/Th17 response","volume":"8","author":"Lavoie","year":"2019","journal-title":"Elife"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05063-7","article-title":"Association between insertion mutation inNOD2 gene and Crohn\u2019s disease in German and British populations","volume":"357","author":"Hampe","year":"2001","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3176","article-title":"High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis","volume":"47","author":"Goyette","year":"2015","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab017","article-title":"Trans-ethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals shared but also ethnicity-specific disease associations","volume":"30","author":"Degenhardt","year":"2021","journal-title":"Hum Mol Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042320-021020","article-title":"The gut microbiome and inflammatory bowel diseases","volume":"73","author":"Shan","year":"2022","journal-title":"Annu Rev Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1136\/gutjnl-2022-327845","article-title":"Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study","volume":"72","author":"Faye","year":"2023","journal-title":"Gut"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8383","DOI":"10.1038\/s41467-024-52195-8","article-title":"Risk of inflammatory bowel disease following hospitalisation with infectious mononucleosis: nationwide cohort study from Denmark","volume":"15","author":"Ebert","year":"2024","journal-title":"Nat Commun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2020.04.013","article-title":"Escherichia coli\u2013specific CD4+ T cells have public T-cell receptors and low interleukin 10 production in crohn\u2019s disease","volume":"10","author":"Uchida","year":"2020","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02556-5","article-title":"Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn\u2019s disease","volume":"29","author":"Martini","year":"2023","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-325373","article-title":"A novel unconventional T cell population enriched in Crohn\u2019s disease","volume":"71","author":"Rosati","year":"2022","journal-title":"Gut"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae190.0299","article-title":"P0125 Crohn\u2019s-associated invariant T Cells are associated with disease severity and location and are not affected by medication intake","volume":"19","author":"Mahdy","year":"2025","journal-title":"J Crohns Colitis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.immuni.2023.04.017","article-title":"Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures","volume":"56","author":"Bourgonje","year":"2023","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2025.01.247","article-title":"Epstein-barr virus (EBV) exposure precedes crohn`s disease development","volume":"169","author":"Nandy","year":"2025","journal-title":"Gastroenterology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaf048","article-title":"Antigen-driven expansion of public clonal T cell populations in inflammatory bowel diseases","volume":"19","author":"Pesesky","year":"2025","journal-title":"J Crohns Colitis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae190.0011","article-title":"OP11 Analysing the T cell receptor beta chain repertoire of 2,800 Inflammatory Bowel Disease patients identifies public T cell responses involved in the pathogenesis of Crohn\u2019s Disease and Ulcerative Colitis and quantifies the impact of surgery and therapy on the immune repertoire of IBD patients","volume":"19","author":"Elabd","year":"2025","journal-title":"J Crohns Colitis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103337","article-title":"Bulk T cell repertoire sequencing (TCR-Seq) is a powerful technology for understanding inflammation-mediated diseases","volume":"149","author":"Mahdy","year":"2024","journal-title":"J Autoimmun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-09140-2","article-title":"T cell receptor clonotypes predict human leukocyte antigen allele carriage and antigen exposure history","volume":"9","author":"ElAbd","year":"2026","journal-title":"Commun Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03692-w","article-title":"T and B\u2009cell responses against Epstein\u2013Barr virus in primary sclerosing cholangitis","volume":"31","author":"ElAbd","year":"2025","journal-title":"Nat Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317878","article-title":"T cell clonal expansions in ileal Crohn\u2019s disease are associated with smoking behaviour and postoperative recurrence","volume":"68","author":"Allez","year":"2019","journal-title":"Gut"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab232.086","article-title":"DOP47 Identification and characterization of T-cell receptor sequences associated with Crohn\u2019s Disease","volume":"16","author":"Pesesky","year":"2022","journal-title":"J Crohns Colitis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000752","article-title":"Characterization of T-cell receptor repertoire in inflamed tissues of patients with crohn\u2019s disease through deep sequencing","volume":"22","author":"Chapman","year":"2016","journal-title":"Inflammation Bowel Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx012","article-title":"Profoundly expanded T-cell clones in the inflamed and uninflamed intestine of patients with crohn\u2019s disease","volume":"11","author":"Doorenspleet","year":"2017","journal-title":"J Crohns Colitis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1595-3","article-title":"Analysis of the B cell receptor repertoire in six immune-mediated diseases","volume":"574","author":"Bashford-Rogers","year":"2019","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e20220538","DOI":"10.1084\/jem.20220538","article-title":"Remodeling of colon plasma cell repertoire within ulcerative colitis patients","volume":"220","author":"Scheid","year":"2023","journal-title":"J Exp Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaf009","article-title":"The multi-organ landscape of B cells highlights dysregulated memory B cell responses in Crohn\u2019s disease","volume":"12","author":"Chen","year":"2025","journal-title":"Natl Sci Rev"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.1038\/s41467-025-58977-y","article-title":"Disease-specific B cell clones are shared between patients with Crohn\u2019s disease","volume":"16","author":"Kotagiri","year":"2025","journal-title":"Nat Commun"},{"key":"B28","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1080\/00365521.2021.1922746","article-title":"Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway","volume":"56","author":"Kristensen","year":"2021","journal-title":"Scand J Gastroenterol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0025-6","article-title":"PhIP-Seq characterization of serum antibodies using oligonucleotide-encoded peptidomes","volume":"13","author":"Mohan","year":"2018","journal-title":"Nat Protoc"},{"key":"B31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13073-025-01486-w","article-title":"Associations between HLA-II variation and antibody specificity are predicted by antigen properties","volume":"17","author":"Innocenti","year":"2025","journal-title":"Genome Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2025.05.13.653535","DOI":"10.1101\/2025.05.13.653535","article-title":"Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing","author":"Mahdy","year":"2025","journal-title":"bioRxiv"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq2422","article-title":"Systemic antibody responses against human microbiota flagellins are overrepresented in chronic fatigue syndrome patients","volume":"8","author":"Vogl","year":"2024","journal-title":"Sci Adv"},{"key":"B34","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s40168-024-01858-1","article-title":"Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn\u2019s disease and chronic fatigue syndrome","volume":"12","author":"Bourgonje","year":"2024","journal-title":"Microbiome"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01409-3","article-title":"Population-wide diversity and stability of serum antibody epitope repertoires against human microbiota","volume":"27","author":"Vogl","year":"2021","journal-title":"Nat Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.524413","article-title":"The usage of human IGHJ genes follows a particular non-random selection: the recombination signal sequence may affect the usage of human IGHJ genes","volume":"11","author":"Shi","year":"2020","journal-title":"Front Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-275859","article-title":"High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations","volume":"116","author":"Wu","year":"2010","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1511","article-title":"Immunoglobulin light chain repertoire in chronic lymphocytic leukemia","volume":"106","author":"Stamatopoulos","year":"2005","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/biology11020161","article-title":"Next-generation sequencing revealed a distinct immunoglobulin repertoire with specific mutation hotspots in acute myeloid leukemia","volume":"11","author":"Xia","year":"2022","journal-title":"Biol (Basel)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2105261","article-title":"Comparative global B cell receptor repertoire difference induced by SARS-CoV-2 infection or vaccination via single-cell V(D)J sequencing","volume":"11","author":"He","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2119\/2006-00080.Ghiotto","article-title":"Similarities and differences between the light and heavy chain ig variable region gene repertoires in chronic lymphocytic leukemia","volume":"12","author":"Ghiotto","year":"2006","journal-title":"Mol Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.07.004","article-title":"Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen","volume":"76","author":"Foster","year":"2016","journal-title":"Mol Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160103","article-title":"B-cell dysregulation in crohn\u2019s disease is partially restored with infliximab therapy","volume":"11","author":"Timmermans","year":"2016","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1056","article-title":"The Patent and Literature Antibody Database (PLAbDab): an evolving reference set of functionally diverse, literature-annotated antibody sequences and structures","volume":"52","author":"Abanades","year":"2024","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1725813\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:55:37Z","timestamp":1770360937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1725813\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2026.1725813"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1725813","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]},"article-number":"1725813"}}