Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus

Transl Stroke Res. 2014 Aug;5(4):510-8. doi: 10.1007/s12975-013-0295-9. Epub 2013 Oct 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Platelets / chemistry*
  • Brain Ischemia / complications
  • Brain Ischemia / epidemiology*
  • Cohort Studies
  • Complement C4b / analysis*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / mortality*
  • Male
  • Middle Aged
  • Peptide Fragments / analysis*
  • Retrospective Studies
  • Stroke / complications
  • Stroke / epidemiology*


  • Biomarkers
  • Peptide Fragments
  • Complement C4b
  • complement C4d