Complement deposition, C4d, on platelets is associated with vascular events in systemic lupus erythematosus

Rheumatology (Oxford). 2020 Nov 1;59(11):3264-3274. doi: 10.1093/rheumatology/keaa092.


Objective: Complement components, including C4d, can be found on activated platelets, a process associated with vascular disease in 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.

Methods: This cross-sectional study included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analysed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). aPL were determined by Luminex, and the LA test was performed by DRVVT. History of vascular disease (composite and as separate outcomes) was defined at inclusion.

Results: SLE patients had increased PC4d deposition as compared with population controls (50 vs 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 (odds ratio: 2.3, 95% CI: 1.3, 4.3, P = 0.008). Compared with patients negative for both PC4d and LA, patients with double positivity were more likely to have vascular disease (odds ratio: 12.3, 95% CI: 5.4, 29.3; attributable proportion due to interaction 0.8, 95% CI: 0.4, 1.1).

Conclusion: 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.

Keywords: C4d; antibodies; antiphospholipid syndrome; risk factors; systemic lupus erythematosus; vascular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantigens / analysis
  • Biomarkers / analysis
  • Blood Platelets / immunology*
  • Carotid Artery Diseases / diagnostic imaging
  • Case-Control Studies
  • Complement Activation
  • Complement C4b / analysis*
  • Cross-Sectional Studies
  • Female
  • Flow Cytometry
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Odds Ratio
  • Peptide Fragments / analysis*
  • Ribonucleoproteins / analysis
  • Risk Factors
  • SS-B Antigen
  • Vascular Diseases / etiology
  • Vascular Diseases / immunology*


  • Autoantigens
  • Biomarkers
  • Peptide Fragments
  • Ribonucleoproteins
  • Complement C4b
  • complement C4d