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By investigating the T cell receptor repertoire of individuals with IBD, novel therapeutic and preventive strategies can be identified, and a better understanding of IBD can be obtained.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To identify and validate T cell clonotypes implicated in the pathogenesis of IBD, we profiled the T cell receptor alpha (TRA) repertoire of three cohorts containing treatment-naive, treated individuals, and individuals living with the disease for &gt;20 years, resulting in an exhaustive dataset containing the TRA repertoire of 1,732 individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using the generated datasets, we were able to replicate previous findings describing the expansion of Crohn\u2019s-associated invariant T (CAIT) cells in individuals with Crohn\u2019s disease (CD) in the three cohorts. Using a hypothesis-free statistical testing framework, we identified clonotypes that were associated with the disease at its different stages,\n                      <jats:italic>e.g.,<\/jats:italic>\n                      at the time of diagnosis and decades post-diagnosis. By conducting a meta-analysis across the three cohorts, we were able to identify a set of clonotypes that were associated with the disease regardless of its stage. We validated our findings in a previously published independent test dataset from a German cohort, showing the robustness of the identified clonotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The identified clonotypes are novel therapeutic targets to treat IBD, for example, through targeted depletion. By identifying antigens recognized by these T cells, a better understanding of the etiopathology of IBD, particularly CD, can be obtained.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-025-01575-w","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T11:02:32Z","timestamp":1767956552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multi-centered T cell repertoire profiling identifies alterations in the immune repertoire of individuals with inflammatory bowel disease across different disease stages"],"prefix":"10.1186","volume":"18","author":[{"given":"Aya K. 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The IBSEN and IBSEN-III study was approved by the South-Eastern Regional Committee for Medical and Health Research Ethics (Ref: 2010\/1540 and 2015\/946-3, respectively) and performed in accordance with the Declaration of Helsinki. As per the Declaration of Helsinki, written informed consent was obtained from participants in accordance with local research ethics committee approvals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approvals and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MP, DM, BH, and HR acknowledge employment by, and equity ownership in, Adaptive Biotechnologies Corp. H.E. did an internship at Adaptive Biotechnologies from July 2023 to September 2023. JH has received consulting and\/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Index Pharma, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB; and speaker\u2019s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma; and research grant support from Janssen, Merck Sharp & Dohme and Takeda. G.P. has served as a speaker and\/or advisory board member for AbbVie. She has also received grant support from Ferring, Tillotts Pharma, and Takeda. V.A.K. received speaker honoraria from Thermo Fischer Scientific, is a consultant for Janssen-Cilag AS, and is on the advisory Board of Tillotts Pharma AG and Takeda AS. J.R.H. received a research grant from Biogen and speaker honoraria from Roche, Novartis, Amgen, and has been a consultant for Novartis and Orkla Health, all unrelated to the present work. M.L.H. received investigator-initiated research grants from Takeda, Pfizer, Tilllotts, Ferring, and Janssen. Speaker honoraria from Takeda, Tillotts, Ferring, AbbVie, Galapagos, and Meda. She is also on the advisory board of Takeda, Galapagos, MSD, Lilly, and AbbVie. All other co-authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}