{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:25:52Z","timestamp":1788585952794,"version":"build-2803163510"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":64,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["vs1-175545,FDN-143301,FDN 143250,GA2-177716,GA1-177703,FBD 187492"],"award-info":[{"award-number":["vs1-175545,FDN-143301,FDN 143250,GA2-177716,GA1-177703,FBD 187492"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","award":["ACG,THW"],"award-info":[{"award-number":["ACG,THW"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Juan and Stefania Speck","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Anti-TNF biologics are widely used to treat patients with immune-mediated inflammatory diseases. In mouse models, the complete absence of TNF impairs germinal center (GC) responses. Less is known about the impact of anti-TNF therapy on specific immune responses in humans. Widespread vaccination against SARS-CoV-2 offered an unprecedented opportunity to investigate the effects of biological therapies on responses to specific immunization. Previous work demonstrated that patients with inflammatory bowel disease (IBD) who were treated with anti-TNF biologics exhibited decreased Spike-specific antibody responses compared with patients with IBD treated with anti-IL-12\/23 or healthy controls, even after 4 doses of mRNA vaccine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Here we analyzed humoral responses to SARS-CoV-2 immunization using single-cell RNA-Sequencing and flow cytometry of Spike-specific memory B cells (MBC), as well as avidity measurements of plasma antibodies from patients with IBD treated with anti-TNF or anti-IL-12\/23 and from people in the healthy control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We observed decreased somatic hypermutation in the B cell receptors of Spike-specific MBCs and decreased antigen-specific MBC accumulation following SARS-CoV-2 mRNA vaccination in patients with IBD treated with anti-TNF, compared with patients with IBD treated with anti-IL-12\/23 or people in the healthy control group. This decreased somatic hypermutation in Spike-specific MBCs in patients treated with anti-TNF correlated with decreased and delayed antibody affinity maturation and reduced neutralization activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These data provide in vivo evidence that anti-TNF, but not anti-IL-12\/23, therapy impairs the quantity and quality of antigen-specific GC outputs in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Juan and Stefania Speck (donation) and by Canadian Institutes of Health Research (CIHR)\/COVID-Immunity Task Force (CITF) grants VR-1 172711, VS1-175545, GA2-177716, GA1-177703 and CIHR FDN 143301 &amp;143350.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci192589","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:00:26Z","timestamp":1753804826000},"source":"Crossref","is-referenced-by-count":5,"title":["Reduced vaccine-induced germinal center outputs in patients with inflammatory bowel disease treated with anti-TNF biologics"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-9914","authenticated-orcid":true,"given":"Michelle W.","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-2506","authenticated-orcid":true,"given":"Janna R.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freda","family":"Qi","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Delgado-Brand","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Colwill","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya M.","family":"Dayam","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny D.","family":"Lee","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M.","family":"Stempak","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-2409","authenticated-orcid":true,"given":"James M.","family":"Rini","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada."},{"name":"Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-0275","authenticated-orcid":true,"given":"Vinod","family":"Chandran","sequence":"additional","affiliation":[{"name":"Gladman Krembil Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada."},{"name":"Division of Rheumatology, Department of Medicine,"},{"name":"Department of Laboratory Medicine and Pathobiology,"},{"name":"Institute of Medical Science, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."},{"name":"Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."},{"name":"Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6090-4437","authenticated-orcid":true,"given":"Anne-Claude","family":"Gingras","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-4890","authenticated-orcid":true,"given":"Tania H.","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.091461"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102193"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103410"},{"key":"B4","unstructured":"Generics and Biosimilars Initiative. Top nine biological drugs by sales in 2023. https:\/\/gabionline.net\/reports\/top-nine-biological-drugs-by-sales-in-2023 Accessed August 13, 2025"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.12.025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.02.002"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020297"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300190"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159721"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28517-z"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28063"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-002008"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11091411"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104788"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/all.16241"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/ar3542"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjad182"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.077552"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201270"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00965.x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-120419-022408"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.004"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.1.159"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.688"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900404"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02458"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102627"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132203"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200922"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abm9060"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43504-8"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.006"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.01.007"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI157250"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112378"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.9.1691"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.979060"},{"key":"B39","doi-asserted-by":"crossref","unstructured":"Vastrad B, Vastrad C. Identification of differentially expressed genes and enriched pathways in inflammatory bowel disease using bioinformatics and next generation sequencing data analysis[preprint]. https:\/\/doi.org\/10.1101\/2023.06.01.543204 Posted on bioRxiv June 5, 2023","DOI":"10.1101\/2023.06.01.543204"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0848-1"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3562"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202217341"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nri3383"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.05.008"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2307\/1934352"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa739"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00358"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.20172"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168344"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02423"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2020.10.009"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.595297"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.240"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01215-y"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159618"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-59535-0"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.07.001"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110242"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.605170"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.165299"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109604"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.03.019"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04527-1"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142362"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601850"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009885"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki010"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1380"},{"key":"B74","unstructured":"Elzhov TV, et al. minpack.lm: R Interface to the Levenberg-Marquardt Nonlinear Least-Squares Algorithm Found in MINPACK, Plus Support for Bounds. Version 1.2-4. https:\/\/cran.r-project.org\/web\/packages\/minpack.lm\/index.html Accessed August 13, 2025"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/192589\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:12:08Z","timestamp":1779210728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/192589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":74,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10,1]]},"published-print":{"date-parts":[[2025,10,1]]}},"alternative-id":["10.1172\/JCI192589"],"URL":"https:\/\/doi.org\/10.1172\/jci192589","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]},"article-number":"e192589"}}