Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis

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,...

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Authors: Zamora, Carlos|||0000-0003-2962-678X, Diaz-Torne, Cesar|||0000-0001-6275-7699, Ortiz, M. Àngels|||0000-0002-1574-9861, Moya, Patricia|||0000-0001-8339-5420, Park, Hye S.|||0000-0002-4972-9527, Pitarch, C., Cantó, Elisabet|||0000-0002-1782-1855, Osuna Gómez, Rubén|||0000-0003-2875-4405, Mulet Gual, Maria|||0000-0003-3639-3291, García-Arguinzonis, Maisa|||0000-0001-6749-5026, Collado, D., Corominas, Hèctor|||0000-0002-7738-6787, Vidal, Silvia|||0000-0002-3909-6682
Format: article
Publication Date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:322589
Online Access:https://ddd.uab.cat/record/322589
https://dx.doi.org/urn:doi:10.3390/cells14090625
Access Level:Open access
Keyword:CD40L
T lymphocyte activation
Cytokine production
Platelet immunomodulation
Rheumatoid arthritis
Description
Summary: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 IFNγ and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFNγ 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 IFNγ 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.

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