Abstract
Objective Complement components, including C4d, can be found on activated platelets, a process associated with vascular disease in systemic lupus erythematosus (SLE). We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease.
Method This cross-sectional study, included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analyzed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). Antiphospholipid antibodies (aPL) were determined by Luminex, and the lupus anticoagulant (LA) test was performed by the DRVVT test. History of vascular disease (composite and as separate outcomes) was defined at inclusion.
Results SLE patients had increased PC4d deposition as compared to population controls (50% versus 5%, p<0.0001). PC4d+ positively associated with any vascular events, and separately with venous and cerebrovascular events, and also with all investigated aPL profiles. The association for any vascular event remained statistically significant after adjustment for traditional and SLE-associated risk factors (OR:2.4, 95% CI 1.3–4.6, p=0.006). Compared to patients negative for both PC4d and LA, patients with double positivity were more likely to have vascular disease (OR:12.0, 95% CI 5.4–28.3; attributable proportion due to interaction 0.7, 95% CI 0.4–1.1) (figure 1).
Interaction analysis between PC4d and Lupus Anticoagulant Interaction between complement C4d deposition (PC4d) and lupus anticoagulant (LA), after adjustment for age (in 10 years), sex, hypertension, estimated glomerular filstration rate (eGFR) according to Modification of Diet in renal Disease (MDRD, per 10 units), and smoking, on the odds of vascular disease (arterial and/or venous) in individuals with systemic lupus erythematosus. RERI = relative excess risk due to interaction; AP = attributable proportion due to interaction. See supplementary material for figures.
Conclusions PC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.
