Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
Por:
Zamora, C, Diaz-Torne, C, Ortiz, MA, Moya, P, Park, HS, Pitarch, C, Cantó, E, Osuna-Gomez, R, Mulet, M, Garcia-Arguinzonis, M, Collado, D, Corominas, H, Vidal, S
Publicada:
22 abr 2025
Resumen:
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 gamma and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFN gamma 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 gamma 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.
Filiaciones:
Zamora, C:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
Diaz-Torne, C:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08041, Spain
Ortiz, MA:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
Moya, P:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08041, Spain
Park, HS:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08041, Spain
Pitarch, C:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08041, Spain
Cantó, E:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
Osuna-Gomez, R:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
Mulet, M:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
Garcia-Arguinzonis, M:
Hosp St Pau IIB St Pau, Inst Recerca, Barcelona 08041, Spain
Collado, D:
Ctr Med Teknon, Barcelona 08022, Spain
Corominas, H:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08041, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain
Vidal, S:
Hosp St Pau IIB St Pau, Inst Recerca, Inflammatory Dis, Barcelona 08041, Spain
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