title: Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus.
abstract: Systemic 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.
authors: Lupus Center of Excellence, Allegheny Health Network, North Tower, Suite 2600, 4800 Friendship Avenue, Pittsburgh, PA, 15224, USA, ahk7@alumni.pitt.edu.
authors: Amy H
authors: AH
authors: Kao
authors: Christine A
authors: CA
authors: McBurney
authors: Abdus
authors: A
authors: Sattar
authors: Apinya
authors: A
authors: Lertratanakul
authors: Nicole L
authors: NL
authors: Wilson
authors: Sarah
authors: S
authors: Rutman
authors: Barbara
authors: B
authors: Paul
authors: Jeannine S
authors: JS
authors: Navratil
authors: Andrea
authors: A
authors: Scioscia
authors: Joseph M
authors: JM
authors: Ahearn
authors: Susan
authors: S
authors: Manzi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry*; D002545:Brain Ischemia / Q000150:complications / Q000453:epidemiology*; D015331:Cohort Studies; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D012189:Retrospective Studies; D020521:Stroke / Q000150:complications / Q000453:epidemiology*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d