Potential for glomerular C4d as an indicator of thrombotic microangiopathy in lupus nephritis

Arthritis Rheum. 2008 Aug;58(8):2460-9. doi: 10.1002/art.23662.


Objective: In patients with systemic lupus erythematosus (SLE) and lupus nephritis, the presence of antiphospholipid antibodies (aPL) is considered to be an indication of increased risk of thrombotic microangiopathy, a serious complication of SLE. Previous studies have demonstrated a critical role for activation of the classical pathway of complement that leads to thrombotic injury in the presence of aPL. This study was undertaken to investigate whether C4d deposition in lupus nephritis is related to circulating aPL and the presence of renal microthrombi.

Methods: Deposition patterns of C4d in 44 renal biopsy samples obtained from 38 patients with biopsy-proven lupus nephritis were determined by staining with a polyclonal anti-C4d antibody. A phosphotungstic acid-hematoxylin stain was used to identify fibrin microthrombi. Clinical data (serum creatinine levels and presence or absence of aPL) were obtained and correlated with findings in the renal biopsy specimens. Patients were categorized as having aPL (n = 20) or not having aPL (n = 18).

Results: A strong relationship between the intensity of glomerular C4d staining and the presence of microthrombi was found (P < 0.002). Intense glomerular C4d deposition was present in 7 of 8 biopsy samples showing renal microthrombi. Neither C4d deposition nor the presence of microthrombi was correlated with aPL status.

Conclusion: Our findings suggest that activation of the classical pathway of complement plays a pathogenic role in the development of renal tissue injury leading to thrombosis, irrespective of the type of circulating antibodies present. Immunodetection of glomerular C4d deposition in renal biopsy samples could be a convenient method of identifying patients at risk of thrombotic microangiopathy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Antiphospholipid / blood
  • Biomarkers / metabolism
  • Biopsy
  • Complement C1q / metabolism
  • Complement C3 / metabolism
  • Complement C4b / metabolism*
  • Female
  • Humans
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / metabolism
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Lupus Nephritis / diagnosis*
  • Lupus Nephritis / metabolism
  • Lupus Nephritis / pathology
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism*
  • Retrospective Studies
  • Thrombosis / diagnosis*
  • Thrombosis / metabolism
  • Thrombosis / pathology
  • Vascular Diseases / diagnosis*
  • Vascular Diseases / metabolism
  • Vascular Diseases / pathology


  • Antibodies, Antiphospholipid
  • Biomarkers
  • Complement C3
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Peptide Fragments
  • Complement C1q
  • Complement C4b
  • complement C4d