{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:34:45Z","timestamp":1785285285422,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III and Fondos FEDER","doi-asserted-by":"publisher","award":["PI20\/184"],"award-info":[{"award-number":["PI20\/184"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, and ELISA, we compared PLTs from HD and RA patients and their effects on T lymphocyte activation and cytokine production. Results: HD PLTs suppressed T lymphocyte proliferation and IFN\u03b3 and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFN\u03b3 levels correlated with T lymphocyte proliferation, greater disease activity, and anti-citrullinated protein antibodies (ACPA). Proteomic analysis revealed that RA PLTs show upregulation of proteins linked to acute-phase response and complement activation. RA PLTs secreted higher levels of soluble CD40L (sCD40L) and PDGF-BB that correlated with enhanced IFN\u03b3 production. Seropositive RA patients had higher levels of sCD40L, and these levels were predictive of disease remission in RA patients treated with anti-IL6R. sCD40L was found to enhance T lymphocyte activation and to contribute to increased pro-inflammatory cytokine production. Conclusions: This study highlights the diminished ability of RA PLTs to suppress T lymphocyte activation and that sCD40L can be a potential biomarker and therapeutic target in RA.<\/jats:p>","DOI":"10.3390\/cells14090625","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"14","author":[{"given":"Carlos","family":"Zamora","sequence":"first","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6275-7699","authenticated-orcid":false,"given":"Cesar","family":"Diaz-Torne","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-9861","authenticated-orcid":false,"given":"Maria Angels","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-5420","authenticated-orcid":false,"given":"Patricia","family":"Moya","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sang","family":"Park","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3","family":"Pitarch","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Cant\u00f3","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-4405","authenticated-orcid":false,"given":"Ruben","family":"Osuna-Gomez","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-3291","authenticated-orcid":false,"given":"Maria","family":"Mulet","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisa","family":"Garcia-Arguinzonis","sequence":"additional","affiliation":[{"name":"Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Collado","sequence":"additional","affiliation":[{"name":"Centre Medic Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7738-6787","authenticated-orcid":false,"given":"Hector","family":"Corominas","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"},{"name":"Department of Medicine, Universitat Autonoma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-6682","authenticated-orcid":false,"given":"Silvia","family":"Vidal","sequence":"additional","affiliation":[{"name":"Inflammatory Diseases, Institut Recerca Hospital Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar2412","article-title":"T cells in rheumatoid arthritis","volume":"10","author":"Cope","year":"2008","journal-title":"Arthritis Res. 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