ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: FR-PO814

Complement in Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation


  • Nikolopoulou, Aikaterini K., Imperial College London, London, United Kingdom
  • Cook, H. Terence, Imperial College of London, London, United Kingdom
  • Pickering, Matthew C., Imperial College London, London, United Kingdom
  • Pusey, Charles D., Imperial College London, London, United Kingdom

Approximately 70% of patients with membranous nephropathy (MN) have autoantibodies against the PLA2 receptor and biopsy specimens generally show positivity for C3 and IgG4 in immune deposits. However the pathway of complement activation in MN remains unclear.


We examined a cohort of patients with PLA2R positive (n=10) and negative (n=9) idiopathic MN. Cases of secondary MN were excluded. Biopsies were stained for PLA2R, complement components (C3c, C3d, C4d, C5b9, FHR5) and IgG4. Staining intensities were graded categorically as 0, 1+, 2+ and 3+. Electron microscopy was performed and the presence of subepithelial electron dense deposits (EDD) was graded according to the percentage of stage 1 and 2 EDD present. More than 80% of stage 1 and 2 EDD was marked 3+, 50-80% was marked 2+, less than 50% was 1+ and absent stage 1 and 2 EDD was scored zero.
Clinical and laboratory characteristics were reviewed.


Both cohorts had similar clinical and laboratory characteristics. The PLA2R positive group had intense staining for all complement factors assessed. In contrast, complement staining in the PLA2R negative group was overall less intense. IgG4 staining was strong in PLA2R positive cases but varied in the PLA2R negative cases. In the PLA2R positive group the majority of the EDD were stage 1 and 2 and this was associated with intense staining particularly for C3c, C5b9, FHR5 and IgG4.


We have identified differences in the intensity of staining of complement factors C3c, C3d, C4d, C5b9 and FHR5 between PLA2R positive and negative patients possibly suggesting differences in disease mechanism that could affect prognosis and influence stratification for complement inhibiting therapies.