{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:55Z","timestamp":1787013835147,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL\u20104\u2010signaling along the T helper 2\u2010axis may be instrumental in IgG4 class switching. Recently, repeated SARS\u2010CoV\u20102 mRNA vaccination has been linked to IgG4 skewing. Although widely used immunosuppressive drugs have been shown to only moderately affect humoral responses to SARS\u2010CoV\u20102 mRNA vaccination, the effect on IgG4 switching has not been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we study the impact of such immunosuppressive drugs, including the IL\u20104 receptor\u2010blocking antibody dupilumab, on IgG4 skewing upon repeated SARS\u2010CoV\u20102 mRNA vaccination. Receptor\u2010binding domain (RBD) specific antibody responses were longitudinally measured in 600 individuals, including patients with immune\u2010mediated inflammatory diseases treated with a TNF inhibitor (TNFi) and\/or methotrexate (MTX), dupilumab, and healthy\/untreated controls, after repeated mRNA vaccination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed a substantial increase in the proportion of RBD\u2010specific IgG4 antibodies (median 21%) in healthy\/untreated controls after third vaccination. This IgG4 skewing was profoundly reduced in dupilumab\u2010treated patients (&lt;1%). Unexpectedly, an equally strong suppression of IgG4 skewing was observed in TNFi\u2010treated patients (&lt;1%), whereas MTX caused a modest reduction (7%). RBD\u2010specific total IgG levels were hardly affected by these immunosuppressive drugs. Minimal skewing was observed, when primary vaccination was adenoviral vector\u2010based.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results imply a critical role for IL\u20104\/IL\u201013 as well as TNF in\u00a0vivo IgG4 class switching. These novel findings advance our understanding of IgG4 class switch dynamics, and may benefit humoral tolerance induction strategies, treatment of IgG4 pathologies and mRNA vaccine optimization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16089","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T01:13:35Z","timestamp":1709601215000},"page":"1952-1961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Suppressed\n                    <scp>IgG4<\/scp>\n                    class switching in dupilumab\u2010 and\n                    <scp>TNF<\/scp>\n                    inhibitor\u2010treated patients after\n                    <scp>mRNA<\/scp>\n                    vaccination"],"prefix":"10.1111","volume":"79","author":[{"given":"Anika M.","family":"Valk","sequence":"first","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"},{"name":"Swammerdam Institute for Life Sciences, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4474-545X","authenticated-orcid":false,"given":"Jim B. D.","family":"Keijser","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koos P. J.","family":"van Dam","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen W.","family":"Stalman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luuk","family":"Wieske","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Clinical Neurophysiology St. Antonius Hospital  Nieuwegein The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Steenhuis","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Y. L.","family":"Kummer","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam The Netherlands"},{"name":"Department of Neurology and Neurophysiology, Amsterdam Neuroscience, Amsterdam UMC, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis I.","family":"Spuls","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam Public Health\/Infection and Immunology, Amsterdam UMC, location AMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel W.","family":"Bekkenk","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam Public Health\/Infection and Immunology, Amsterdam UMC, location AMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie H.","family":"Musters","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam Public Health\/Infection and Immunology, Amsterdam UMC, location AMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoline F.","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam Public Health\/Infection and Immunology, Amsterdam UMC, location AMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Bosma","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam Public Health\/Infection and Immunology, Amsterdam UMC, location AMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMCG Expertise Center for Blistering Diseases University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3379-3425","authenticated-orcid":false,"given":"Dirk\u2010Jan","family":"Hijnen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine R. G.","family":"Schreurs","sequence":"additional","affiliation":[{"name":"Department of Dermatology Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00e9 L. E.","family":"van Kempen","sequence":"additional","affiliation":[{"name":"Department of Neurology Amsterdam UMC, VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep","family":"Killestein","sequence":"additional","affiliation":[{"name":"Department of Neurology Amsterdam UMC, VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan G.","family":"Volkers","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC Academic Medical Center, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander W.","family":"Tas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, Academic Medical Center University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boekel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Amsterdam Rheumatology and Immunology Center, Reade  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit J.","family":"Wolbink","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"},{"name":"Department of Rheumatology Amsterdam Rheumatology and Immunology Center, Reade  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Keijzer","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninotska I. 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