Prospective assessment of C4d deposits on circulating cells and renal tissues in lupus nephritis: a pilot study

Lupus. 2012 Jan;21(1):13-26. doi: 10.1177/0961203311422093. Epub 2011 Sep 29.


Complement activation plays a key role in the pathogenesis of lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE). We prospectively evaluated 15 LN subjects and two control groups: 13 non-SLE renal subjects (control A) and 239 SLE subjects without LN (control B). All had C4d levels on circulating erythrocytes (E-C4d), reticulocytes (R-C4d) and platelets (P-C4d) measured by flow cytometry, while C4d deposition in renal tissue was semiquantitatively assessed in LN subjects and control A using immunoperoxidase staining. Compared with control A, LN biopsies had higher glomerular-C4d scores (p = 0.003), which were associated with more frequent granular glomerular immunofluorescence staining and electron dense deposits (p < 0.001). Compared with control A and B groups, LN subjects had higher E-C4d (p = 0.002 and p = 0.005) and R-C4d levels (p = 0.002 and p = 0.008), respectively. LN subjects were more likely to have P-C4d compared with control A (p = 0.016). In LN, only E-C4d correlated with National Institutes of Health (NIH) activity index (r = 0.55, p = 0.04). In conclusion, LN biopsies showed frequent glomerular-C4d staining associated with immune complex deposits. LN subjects had higher E-C4d and R-C4d levels compared with both control groups. E-C4d levels also correlated with NIH activity index. These findings suggest a potential role of C4d on circulating cells as a biomarker for lupus nephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Platelets / pathology*
  • Cohort Studies
  • Complement C4b / immunology*
  • Erythrocytes / pathology*
  • Female
  • Humans
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure
  • Lupus Erythematosus, Systemic / complications
  • Lupus Nephritis / blood*
  • Lupus Nephritis / etiology
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Pilot Projects
  • Prospective Studies
  • Reticulocytes / pathology*
  • Young Adult


  • Biomarkers
  • Peptide Fragments
  • Complement C4b
  • complement C4d