Platelet glycoprotein V autoantibodies and complement C3 are associated with thrombosis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular disease risk not fully explained by traditional factors. This retrospective study investigated the frequency and clinical relevance of platelet-specific glycoprotein (GP) autoantibodies and anti-phospholipid antibodies (aPL) in SLE. Serum from 89 patients with SLE (≥4 American College of Rheumatology 1982 criteria) was analyzed at higher (H) and lower (L) disease activity (median SLEDAI-2K: H=9.6 and L=2.1). Platelet GPIIb/IIIa-, GPV- and GPIb/IX-autoantibodies were detected using the indirect monoclonal antibody immobilization of platelet antigens assay, while immunoglobulin (Ig)M/IgG aPL, anti-β2 glycoprotein 1 (aβ2GP1), anti-cardiolipin (anti-CL), anti-phosphatidylserine/prothrombin complex (anti-PS/PT) and anti-annexin V (anti-AV) antibodies were measured by enzyme-linked immunosorbent assay. At high activity, 64% (57/89) of patients tested positive for at least one anti-GP antibody, compared to 42% (37/89) with low-disease activity. Anti-GPIIb/IIIa prevalence was stable (~30%), whereas anti-GPV and anti-GPIb/IX were more frequent during H (48% [43/89] vs. 24% [21/89] and 49% [44/89] vs. 27% [24/89], respectively). Anti-GPV levels correlated positively with SLEDAI-2K (r=0.34; P=0.001) and negatively with C3 and C4. Twenty-four patients developed unprovoked thromboembolic events during follow-up. In multivariate analysis, anti-GPV and C3 independently predicted thrombosis (hazard ratio [HR]=2.17; 95% confidence interval [CI]: 1.39-3.36; P=0.001; and HR=2.16; 95% CI: 1.32- 3.54; P=0.002). Platelet counts remained within the normal range irrespective of disease activity, antibody status or thrombotic events. In summary, platelet-specific anti-GP antibodies are prevalent in SLE patients. Anti-GPV, previously not studied in this context and complement C3, independently predicted thrombotic events.