Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus

Clin Immunol. 2021 Jul:228:108755. doi: 10.1016/j.clim.2021.108755. Epub 2021 May 11.

Abstract

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4-24.0] vs. 4.0 [2.5-8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = -0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

Keywords: Antiphospholipid syndrome; Autoimmune disease; Biomarker; Cardiovascular disease; Complement split products; Inflammation; Platelet; Systemic lupus erythematosus; Thrombosis.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Autoantibodies / immunology
  • Autoimmunity
  • Biomarkers
  • Blood Platelets / immunology
  • Blood Platelets / metabolism*
  • Complement Activation / immunology*
  • Complement C4 / immunology*
  • Complement C4 / metabolism
  • Disease Susceptibility
  • Humans
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism*
  • Platelet Activation / genetics*
  • Platelet Activation / immunology
  • Platelet Aggregation
  • Platelet Count
  • Thrombosis / etiology
  • Thrombosis / metabolism
  • Vascular Diseases / etiology*
  • Vascular Diseases / metabolism

Substances

  • Autoantibodies
  • Biomarkers
  • Complement C4
  • Adenosine Diphosphate