{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:22:54Z","timestamp":1779290574229,"version":"3.51.4"},"reference-count":22,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"unspecified","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008319","name":"Fondation Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008017","name":"Gustave Roussy","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008017","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondation Malakoff M\u00e9d\u00e9ric"},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-21-RHUS-0013"],"award-info":[{"award-number":["ANR-21-RHUS-0013"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FHU CARE"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,3,13]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Background<\/jats:title>\n Programmed cell death protein 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are immune checkpoints expressed on T cells. Despite recent development of PD-1 agonists in rheumatoid arthritis (RA), little is known about PD-1 and TIGIT coexpression in RA and other immune-mediated inflammatory diseases (IMIDs). This study quantified PD-1 and TIGIT expression in CD4 and CD8 T cells in patients with IMID and examined associations with disease characteristics and anti-tumour necrosis factor (TNF) response.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Biologics-na\u00efve patients with RA and spondyloarthritis (AS) were followed prospectively to assess anti-TNF response at 12 months. Sj\u00f6gren\u2019s disease (SjD) patients and healthy volunteers (HV) were also included at baseline. PD-1 and TIGIT expression on CD4 and CD8 T cells was analysed by flow cytometry at baseline and after 3 months of anti-TNF treatment. Plasma cytokines were quantified using the Meso Scale Discovery assay.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 67 patients were included. Median CD8\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n levels were higher in RA (24%) and SjD (23.2%) than in HV (18.8%) and AS (16.2%). CD4\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n were positively correlated with circulating immunoglobulin G (r=0.698,\u2009p<0.001), interferon gamma (r=0.635, p=0.017) and IP-10 (r=0.612 p=0.005) levels in patients with SjD. Baseline CD4\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n levels were higher in future anti-TNF responders (9.9%) compared with non-responders (6.1%, p=0.003). Both CD4\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n and CD8\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n cells increased after 3 months of anti-TNF treatment in RA and AS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n CD8\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n T-cell expression is elevated in SjD and RA compared with HV and AS. CD4\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n levels are higher in future anti-TNF responders compared with non-responders and rise after treatment in patients with RA and AS. Further studies should clarify the functional role of CD4\n +<\/jats:sup>\n PD-1\n +<\/jats:sup>\n TIGIT\n +<\/jats:sup>\n cells in IMIDs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006537","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:30:17Z","timestamp":1779287417000},"page":"e006537","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["PD1\n +<\/sup>\n TIGIT\n +<\/sup>\n CD4\n +<\/sup>\n T cells predict response to anti-TNF in rheumatoid arthritis and spondyloarthritis"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-2269","authenticated-orcid":false,"given":"Samuel","family":"Bitoun","sequence":"first","affiliation":[{"name":"Rheumatology Department, Universit\u00e9 Paris-Saclay, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR1184, H\u00f4pital Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris (APHP), CEA, FHU CARE 2, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Roulleaux-Dugage","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunomonitoing en Oncologie US23, Bioth\u00e9rapies Innovantes U1363, Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Villejuif, France"},{"name":"D\u00e9partement d\u2019Innovation Th\u00e9rapeutique et d\u2019Essais Pr\u00e9coces (DITEP), Universit\u00e9 Paris-Saclay, Gustave Roussy, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Naigeon","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunomonitoing en Oncologie US23, Bioth\u00e9rapies Innovantes U1363, Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9922-607X","authenticated-orcid":false,"given":"Caroline","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunomonitoing en Oncologie US23, Bioth\u00e9rapies Innovantes U1363, Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Berthot","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunomonitoing en Oncologie US23, Bioth\u00e9rapies Innovantes U1363, Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-5417","authenticated-orcid":false,"given":"Xavier","family":"Mariette","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Universit\u00e9 Paris-Saclay, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR1184, H\u00f4pital Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris (APHP), CEA, FHU CARE 2, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-0733","authenticated-orcid":false,"given":"Gaetane","family":"Nocturne","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Universit\u00e9 Paris-Saclay, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR1184, H\u00f4pital Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris (APHP), CEA, FHU CARE 2, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Chaput","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunomonitoing en Oncologie US23, Bioth\u00e9rapies Innovantes U1363, Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"2026052007301159000_12.2.e006537.1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature New 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Citrullinated Vimentin-reactive Immuneregulatory CD4+CD39+TIGIThi T cells expand during drug free remission in HLA-DR shared-epitope+ ACPA+ Rheumatoid Arthritis. 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