{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:31:31Z","timestamp":1791563491578,"version":"4.3.4"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"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:sec><jats:title>Background<\/jats:title><jats:p>Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1\/2), ruxolitinib (JAK1\/2), upadacitinib (JAK1\/2) as well as filgotinib (selective JAK1) on <jats:italic>in-vitro<\/jats:italic> B cell activation, proliferation, and class switch recombination and involved pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an <jats:italic>in-vitro<\/jats:italic> model of T-cell-independent B cell activation we observed that JAK1\/2 and selective JAK1 inhibitor treatment led to a dose-dependent decrease of total B cell numbers. We detected an altered B cell differentiation with a significant increase in MZ-like B cells and an increase in plasmablast differentiation in the first days of culture, most pronounced with the pan-JAK inhibitor tofacitinib, although there was no increase in immunoglobulin secretion <jats:italic>in-vitro<\/jats:italic>. Notably, we further observed a profound reduction of switched memory B cell formation, especially with JAK1\/2 inhibition. JAK inhibitor treatment led to a dose-dependent reduction of STAT3 expression and phosphorylation as well as STAT3 target gene expression and modulated the secretion of pro- and anti-inflammatory cytokines by B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>JAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1087986","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:49:58Z","timestamp":1674708598000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with\u00a0rheumatoid arthritis"],"prefix":"10.3389","volume":"14","author":[{"given":"Natalie","family":"Frede","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Lorenzetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janika M","family":"H\u00fcppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iga","family":"Janowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Troilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marei-Theresa","family":"Schleyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Venhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard E.","family":"Voll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Thiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Venhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005033221805.","article-title":"Rheumatoid arthritis. pathophysiology and implications for therapy","volume":"322","author":"Harris","year":"1990","journal-title":"N Engl J Med"},{"key":"B2","article-title":"Taking mortality in rheumatoid arthritis seriously\u2013predictive markers, socioeconomic status and comorbidity","volume":"13","author":"Pincus","year":"1986","journal-title":"J Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.autrev.2011.06.010","article-title":"B-cells and their targeting in rheumatoid arthritis\u2013current concepts and future perspectives","volume":"11","author":"Nakken","year":"2011","journal-title":"Autoimmun Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205428","article-title":"Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA","volume":"74","author":"Hecht","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.04.016","article-title":"Abatacept modulates CD80 and CD86 expression and memory formation in human b-cells","volume":"101","author":"Lorenzetti","year":"2019","journal-title":"J Autoimmun"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.144.9.3347","article-title":"Quantitative analysis of cytokine gene expression in rheumatoid arthritis","volume":"144","author":"Firestein","year":"1990","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.068064","article-title":"Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): Evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab","volume":"66","author":"Nishimoto","year":"2007","journal-title":"Ann Rheum Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.9.768","article-title":"Tumour necrosis factor in synovial exudates","volume":"47","author":"Di Giovine","year":"1988","journal-title":"Ann Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(99)05246-0","article-title":"Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: A randomised phase III trial","volume":"354","author":"Maini","year":"1999","journal-title":"ATTRACT Study Group Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032534","article-title":"Efficacy of b-cell-targeted therapy with rituximab in patients with rheumatoid arthritis","volume":"350","author":"Edwards","year":"2004","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048922","article-title":"JAK inhibitors: Ten years after","volume":"51","author":"Spinelli","year":"2021","journal-title":"Eur J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.10.022","article-title":"The emerging role of janus kinase inhibitors in the treatment of autoimmune and inflammatory diseases","volume":"147","author":"Damsky","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"212595","DOI":"10.7573\/dic.212595","article-title":"Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis","volume":"8","author":"Biggioggero","year":"2019","journal-title":"Drugs Context."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.201","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"16","author":"Schwartz","year":"2017","journal-title":"Nat Rev Drug Discovery"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867","article-title":"IL-21 induces differentiation of human naive and memory b cells into antibody-secreting plasma cells","volume":"175","author":"Ettinger","year":"2005","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5361","article-title":"Regulation of b cell differentiation and plasma cell generation by IL-21, a novel inducer of blimp-1 and bcl-6","volume":"173","author":"Ozaki","year":"2004","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.2.332","article-title":"The essential role of b cell stimulatory factor 2 (BSF-2\/IL-6) for the terminal differentiation of b cells","volume":"167","author":"Muraguchi","year":"1988","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1817","article-title":"Interleukin-6 is a growth factor for nonmalignant human plasmablasts","volume":"97","author":"Jego","year":"2001","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.018","article-title":"Inhibition of human b-cell development into plasmablasts by histone deacetylase inhibitor valproic acid","volume":"131","author":"Kienzler","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/cmi.2011.2","article-title":"Marginal zone b cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis","volume":"8","author":"Carnrot","year":"2011","journal-title":"Cell Mol Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700326104","article-title":"Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory b cells","volume":"104","author":"Gray","year":"2007","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546248","article-title":"MZ b cells migrate in a T-bet dependent manner and might contribute to the remission of collagen-induced arthritis by the secretion of IL-10","volume":"46","author":"Huber","year":"2016","journal-title":"Eur J Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02242","article-title":"Marginal-zone b-cells are main producers of IgM in humans, and are reduced in patients with autoimmune vasculitis","volume":"9","author":"Appelgren","year":"2018","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"R108","DOI":"10.1186\/ar3042","article-title":"Decreased frequency and activated phenotype of blood CD27 IgD IgM b lymphocytes is a permanent abnormality in systemic lupus erythematosus patients","volume":"12","author":"Rodr\u00edguez-Bayona","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"B26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s10875-010-9456-8","article-title":"TLR1\/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory b cell subsets to produce cytokines, chemokines, and hematopoietic growth factors","volume":"31","author":"Agrawal","year":"2011","journal-title":"J Clin Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636483","article-title":"TLR-mediated stimulation of APC: Distinct cytokine responses of b cells and dendritic cells","volume":"37","author":"Barr","year":"2007","journal-title":"Eur J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343822","article-title":"Autocrine IL-10 promotes human b-cell differentiation into IgM- or IgG-secreting plasmablasts","volume":"44","author":"Heine","year":"2014","journal-title":"Eur J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130323","article-title":"Naive and memory human b cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells","volume":"210","author":"Deenick","year":"2013","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nri3383","article-title":"Marginal zone b cells: Virtues of innate-like antibody-producing lymphocytes","volume":"13","author":"Cerutti","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3569","article-title":"A role for toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive b cells and constitutive expression in memory b cells","volume":"101","author":"Bernasconi","year":"2003","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.1.277","article-title":"B cell differentiation and isotype switching is related to division cycle number","volume":"184","author":"Hodgkin","year":"1996","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00065","article-title":"Cytokine-mediated regulation of plasma cell generation: IL-21 takes center stage","volume":"5","author":"Moens","year":"2014","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8180","article-title":"Cytokine-mediated regulation of human b cell differentiation into ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells","volume":"179","author":"Bryant","year":"2007","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091706","article-title":"B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans","volume":"207","author":"Avery","year":"2010","journal-title":"J Exp Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903207","article-title":"IL-21 receptor is critical for the development of memory b cell responses","volume":"186","author":"Rankin","year":"2011","journal-title":"J Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111229","article-title":"Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome","volume":"210","author":"Kotlarz","year":"2013","journal-title":"J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190344","article-title":"Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses","volume":"216","author":"Spencer","year":"2019","journal-title":"J Exp Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2305","article-title":"DOCK8 functions as an adaptor that links TLR-MyD88 signaling to b cell activation","volume":"13","author":"Jabara","year":"2012","journal-title":"Nat Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300765","article-title":"IL-21 enhances the activity of the TLR-MyD88-STAT3 pathway but not the classical TLR-MyD88-NF-\u03baB pathway in human b cells to boost antibody production","volume":"191","author":"Liu","year":"2013","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.011","article-title":"STAT5B restrains human b-cell differentiation to maintain humoral immune homeostasis","volume":"150","author":"Pelham","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011205","article-title":"The Jak\/STAT pathway","volume":"4","author":"Harrison","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2008.08.008","article-title":"Canonical and non-canonical JAK-STAT signaling","volume":"18","author":"Li","year":"2008","journal-title":"Trends Cell Biol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/82_2015_479","article-title":"Roles of the NF-\u03baB pathway in b-lymphocyte biology","volume":"393","author":"Sasaki","year":"2016","journal-title":"Curr Top Microbiol Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/s41598-018-19460-5","article-title":"PI3K induces b-cell development and regulates b cell identity","volume":"8","author":"Abdelrasoul","year":"2018","journal-title":"Sci Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2016.1215288","article-title":"The PI3K pathway in b cell metabolism","volume":"51","author":"Jellusova","year":"2016","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804868105","article-title":"A p38 MAPK-MEF2C pathway regulates b-cell proliferation","volume":"105","author":"Khiem","year":"2008","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.4805","article-title":"STAT3-mediated up-regulation of BLIMP1 is coordinated with BCL6 down-regulation to control human plasma cell differentiation","volume":"180","author":"Diehl","year":"2008","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.10.008","article-title":"Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors","volume":"31","author":"Kwon","year":"2009","journal-title":"Immunity"},{"key":"B50","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s13075-019-1964-1","article-title":"Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations","volume":"21","author":"McInnes","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1021\/jm401490p","article-title":"Discovery and development of janus kinase (JAK) inhibitors for inflammatory diseases","volume":"57","author":"Clark","year":"2014","journal-title":"J Med Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201348","article-title":"Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases","volume":"191","author":"Van Rompaey","year":"2013","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1093\/rheumatology\/key339","article-title":"Clinical significance of janus kinase inhibitor selectivity","volume":"58","author":"Choy","year":"2019","journal-title":"Rheumatol (Oxford)."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0419-y","article-title":"Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK 1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis","volume":"55","author":"Mohamed","year":"2016","journal-title":"Clin Pharmacokinet"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219012","article-title":"JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib","volume":"80","author":"Traves","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01303-3","article-title":"Comparative efficacy of JAK inhibitors for moderate-To-Severe rheumatoid arthritis: A network meta-analysis","volume":"37","author":"Pope","year":"2020","journal-title":"Adv Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X21999564","article-title":"Comparative efficacy and safety of janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: A systematic review and network meta-analysis","volume":"13","author":"Weng","year":"2021","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13616","article-title":"Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials","volume":"22","author":"Song","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-020-00750-1","article-title":"Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in patients with active rheumatoid arthritis","volume":"79","author":"Lee","year":"2020","journal-title":"Z Rheumatol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/nrrheum.2017.23","article-title":"The emerging safety profile of JAK inhibitors in rheumatic disease","volume":"13","author":"Winthrop","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X20936059","article-title":"JAK inhibitors and infections risk: focus on herpes zoster","volume":"12","author":"Sunzini","year":"2020","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000001749","article-title":"The risk of infections associated with JAK inhibitors in rheumatoid arthritis: A systematic review and network meta-analysis","volume":"28","author":"Alves","year":"2021","journal-title":"J Clin Rheumatol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210105","article-title":"Filgotinib (GLPG0634\/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)","volume":"76","author":"Kavanaugh","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207191","article-title":"The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis","volume":"75","author":"Winthrop","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B65","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s13075-019-1883-1","article-title":"Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy","volume":"21","author":"Winthrop","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"B66","article-title":"Evaluation of response to pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: Results from a phase 2 open-label extension study. ACR 2020","volume":"72","author":"Winthrop","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00314-3","article-title":"Do JAK inhibitors affect immune response to COVID-19 vaccination? data from the MAJIK-SFR registry","volume":"4","author":"Seror","year":"2021","journal-title":"Lancet Rheumatol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220647","article-title":"Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study","volume":"80","author":"Furer","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B69","article-title":"The mechanism of action of tofacitinib - an oral janus kinase inhibitor for the treatment of rheumatoid arthritis","volume":"34","author":"Hodge","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"B70","unstructured":"FDA Label olumiant2018"},{"key":"B71","unstructured":"FDA Label rinvoq2019"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01439-0","article-title":"Filgotinib: First approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1087986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:50:04Z","timestamp":1674708604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1087986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":72,"alternative-id":["10.3389\/fimmu.2023.1087986"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1087986","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]},"article-number":"1087986"}}