Platelet bound B cells and their role in SSc: Implications for disease subtypes and clinical outcomes

Abstract

Objectives

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular damage, immune dysregulation, and tissue fibrosis. While lymphocyte-platelet (PLT) complexes have been implicated in autoimmune diseases, their role in SSc is not well understood. Methods: In a study of 21 predominantly female SSc patients, 66.7 % had limited SSc (lcSSc), with anti-centromere antibodies (ACA) being the most common autoantibody pattern. We applied flow cytometry to analyze B cells with bound PLTs, enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of activated PLT soluble factors, and co-culture assays to evaluate B cell cytokine secretion and plasma cell differentiation. Results: SSc patients had a higher percentage of B cells, but not T cells, with bound PLTs compared to healthy donors (HD). Despite similar PLT counts, SSc patients showed higher plasmatic levels of P-selectin (CD62P), soluble CD40 ligand (sCD40L), platelet-derived growth factor (PDGF), and transforming growth factor–β (TGF-β). Plasma IL-10 levels were also higher in SSc patients, with increased intracellular IL-10 in B cells with bound PLTs. We observed an increased IL-10 production and plasma cell differentiation when B cells were co-cultured with PLTs, especially from SSc patients. B cells with bound PLTs were associated with calcinosis, digital ulcers, and ACA status, with no effect from previous corticosteroid or aspirin therapy. Logistic regression identified B cells with bound PLTs as a predictor for distinguishing lcSSc patients. Conclusions: B cells with bound PLTs play a significant role in SSc by modulating B cell function and contributing to disease pathogenesis. Their association with clinical parameters suggests their potential as biomarkers for disease severity and subtype classification in SSc.