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

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-OR36

Protocadherin 7-Associated Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
  • Madden, Benjamin J., Mayo Clinic, Rochester, Minnesota, United States
  • Gross, Louann, Mayo Clinic, Rochester, Minnesota, United States
  • Negron, Vivian C., Mayo Clinic, Rochester, Minnesota, United States
  • Charlesworth, Cristine, Mayo Clinic, Rochester, Minnesota, United States
  • Debiec, Hanna, Sorbonne Universite, Paris, Île-de-France, France
  • Ronco, Pierre M., Sorbonne Universite, Paris, France
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
Background

Membranous nephropathy (MN) results from subepithelial antigen-antibody complex deposition along the glomerular basement membrane (GBM). Although PLA2R, THSD7A, and NELL-1 account for a majority (approximately 80%) of the target antigens, the target antigen in the remaining MN is not known.

Methods

We performed laser microdissection and mass spectrometry (MS) of glomeruli in kidney biopsies of 85 cases of PLA2R-negative MN. We detected high spectral counts of a unique protein Protocadherin 7 (PCDH7) in 8 cases. Immunohistochemistry (IHC) for PCDH7 was then performed to confirm MS results.

Results

MS identified a unique protein, PCDH7 in 8 cases (9.4%) of PLA2R-negative MN. MS failed to detect PCDH7 in remaining 77 PLA2R-negative MN, 23 PLA2R-positive MN, and 88 controls that included IgA nephropathy, diabetes, FSGS and minimal change disease. Among the 77 PLA2R-negative MN, MS detected NELL1 (14 cases), EXT1/EXT2 (6 cases), PLA2R (4 cases labeled PLA2R-negative on IF), Sema3B (3 cases), THSD7A (2 cases), and DNAJB9 (4 cases of fibrillary GN, misdiagnosed as MN as EM was not done). PCDH7 localized as granular deposits along the GBM by IHC (Figure 1). Kidney biopsy showed a grade II MN in 6 cases, grade I in 1 and grade III in 1 case. Immunofluorescence microscopy showed GBM staining for IgG and C3 in all cases. IgG subtyping done in 2 cases showed IgG4 in both. The mean age was 64 years (+/- 11) and 7 of the 8 patients were males. The average serum creatinine and proteinuria was 1.28 mg/dL (+/- 0.3) and 4.9 gm/L (+/- 3.0), respectively. Interestingly, 3 of 8 cases had associated malignancies. Further studies including evaluation for circulating antibodies are ongoing.

Conclusion

Protocadherin 7-associated MN may represent distinct type of MN.

Figure 1 shows bright granular capillary wall staining for PCDH7 in 3 cases (A, B, C) of PCDH7-associated MN, and negative staining in a case (D) of PLA2R-negative MN.