• Amy H Kao, Christine A McBurney, Abdus Sattar, Apinya Lertratanakul, Nicole L Wilson, Sarah Rutman, Barbara Paul, Jeannine S Navratil, Andrea Scioscia, Joseph M Ahearn, and Susan Manzi.
• Lupus Center of Excellence, Allegheny Health Network, North Tower, Suite 2600, 4800 Friendship Avenue, Pittsburgh, PA, 15224, USA, ahk7@alumni.pitt.edu.
• Transl Stroke Res. 2014 Aug 1; 5 (4): 510-8.

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease associated with significant morbidity, including premature cardiovascular disease, and mortality. Platelets bearing complement protein C4d (P-C4d) were initially determined to be specific for diagnosis of SLE and were later found to be associated with acute ischemic stroke in non-SLE patients. P-C4d may identify a subset of SLE patients with a worse clinical prognosis. This study investigated the associations of P-C4d with all-cause mortality and vascular events in a lupus cohort. A cohort of 356 consecutive patients with SLE was followed from 2001 to 2009. Primary outcome was all-cause mortality. Secondary outcomes were vascular events (myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, ischemic stroke, venous thromboembolism, pulmonary embolism, or other thrombosis). P-C4d was measured at study baseline. Seventy SLE patients (19.7%) had P-C4d. Mean follow-up was 4.7 years. All-cause mortality was 4%. P-C4d was associated with all-cause mortality (hazard ratio 7.52, 95% confidence interval (CI) 2.14-26.45, p = 0.002) after adjusting for age, ethnicity, sex, cancer, and anticoagulant use. Vascular event rate was 21.6%. Patients with positive P-C4d were more likely to have had vascular events compared to those with negative P-C4d (35.7 vs. 18.2%, p = 0.001). Specifically, P-C4d was associated with ischemic stroke (odds ratio 4.54, 95% CI 1.63-12.69, p = 0.004) after adjusting for age, ethnicity, and antiphospholipid antibodies. Platelet-C4d is associated with all-cause mortality and stroke in SLE patients. P-C4d may be a prognostic biomarker as well as a pathogenic clue that links platelets, complement activation, and thrombosis.

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