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Related Experiment Video

Updated: Nov 9, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Protocadherin 7-Associated Membranous Nephropathy.

Sanjeev Sethi1, Benjamin Madden2, Hanna Debiec3

  • 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Journal of the American Society of Nephrology : JASN
|April 9, 2021
PubMed
Summary

Researchers identified a new cause of membranous nephropathy (MN), a kidney disease. Protocadherin 7 (PCDH7) is a novel antigen implicated in a subset of PLA2R-negative MN cases.

Keywords:
glomerular diseaseimmunology and pathologymembranous nephropathynephrotic syndromerenal biopsyrenal pathology

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Area of Science:

  • Nephrology
  • Immunology
  • Pathology

Background:

  • Membranous nephropathy (MN) is an autoimmune kidney disease characterized by immune complex deposition in the glomeruli.
  • Established target antigens like Phospholipase A2 Receptor (PLA2R) explain most MN cases, but a significant portion remains antigen-negative.

Purpose of the Study:

  • To identify novel target antigens in patients with PLA2R-negative membranous nephropathy.
  • To characterize the clinical and pathological features of MN associated with newly identified antigens.

Main Methods:

  • Laser microdissection and mass spectrometry (MS/MS) were employed on kidney biopsies from 135 PLA2R-negative MN cases.
  • Immunohistochemistry, immunofluorescence, confocal microscopy, Western blot, and serum/tissue elution studies were used for validation and antibody detection.

Main Results:

  • Protocadherin 7 (PCDH7) was identified as a novel antigen in 5.7% of PLA2R-negative MN cases.
  • PCDH7 deposition along the glomerular basement membrane (GBM) was confirmed by immunohistochemistry, co-localizing with IgG.
  • Antibodies against PCDH7 were detected in patient sera and eluted from kidney biopsies.

Conclusions:

  • Membranous nephropathy associated with PCDH7 represents a distinct, previously unrecognized subtype of the disease.
  • PCDH7 is a novel target antigen in a subset of idiopathic MN, expanding the known antigenic targets in this condition.