{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:42:30Z","timestamp":1791520950281,"version":"4.3.4"},"reference-count":37,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie","award":["860003"],"award-info":[{"award-number":["860003"]}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430072010007"],"award-info":[{"award-number":["10430072010007"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARC-DECRA Fellowship","award":["DE220100185"],"award-info":[{"award-number":["DE220100185"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,9,12]]},"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7\u2009days and 3\u20136\u2009months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NL8900.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004664","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T23:05:29Z","timestamp":1728342329000},"page":"e004664","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1575-2973","authenticated-orcid":false,"given":"Laura Y L","family":"Kummer","sequence":"first","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"},{"name":"Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fern\u00e1ndez Blanco","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"},{"name":"Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kreher","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Bos","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisan H","family":"Kuijper","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels J M","family":"Verstegen","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolien E","family":"van de Sandt","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"},{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique A L","family":"Konijn","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebl C","family":"Duurland","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Menage","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke","family":"Jorritsma","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Steenhuis","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth R","family":"Hagen","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jet","family":"van den Dijssel","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"},{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"de Jongh","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Ashhurst","sequence":"additional","affiliation":[{"name":"Cytometry Core Research Facility, The University of Sydney Charles Perkins Centre, Sydney, New South Wales, Australia"},{"name":"The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit J","family":"van Gils","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Garcia-Vallejo","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Claireaux","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9715-0915","authenticated-orcid":false,"given":"Eileen W","family":"Stalman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2602-4364","authenticated-orcid":false,"given":"Koos P J","family":"van Dam","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luuk","family":"Wieske","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands"},{"name":"Department of Clinical Neurophysiology, St Antonius Ziekenhuis, Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-7786","authenticated-orcid":false,"given":"Laura","family":"Boekel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Reade Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-7460","authenticated-orcid":false,"given":"Gertjan","family":"Wolbink","sequence":"additional","affiliation":[{"name":"Sanquin Research, Amsterdam, The Netherlands"},{"name":"Department of Rheumatology, Reade Research, 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 University Medical Centres, Amsterdam, The 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