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A Target Antigen-Based Approach to the Classification of Membranous Nephropathy

Shane A Bobart1, Shahrzad Tehranian2, Sanjeev Sethi3

  • 1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Cleveland Clinic Florida, Weston.

Mayo Clinic Proceedings
|March 6, 2021
PubMed
Abstract

Insights

This study characterizes membranous nephropathy (MN) by target antigen, including PLA2R-associated MN in older men and EXT1/EXT2-associated MN in younger women with autoimmunity. A new classification combining antigen and associated disease is proposed for better MN management.

Area of Science:

  • Nephrology
  • Immunopathology
  • Clinical Medicine

Background:

  • Membranous nephropathy (MN) classification traditionally relies on primary vs. secondary distinctions, which have limitations.
  • Identifying specific target antigens is crucial for understanding MN pathogenesis and clinical presentation.

Purpose of the Study:

  • To describe the clinical and pathological phenotypes of MN associated with various target antigens: PLA2R, THSD7A, SEMA3B, NELL-1, PCDH7, EXT1/EXT2, and NCAM-1.
  • To propose a refined classification system for MN that integrates target antigen and associated diseases.

Main Methods:

  • Retrospective cohort study of 270 adult patients with biopsy-proven MN.
  • Classification of MN based on serologic tests, immunostaining, and/or mass spectrometry for target antigens.
  • Systematic abstraction of clinical, biochemical, pathological, and follow-up data, including associated conditions.

Main Results:

  • PLA2R-associated MN predominantly affected middle-aged white men, with associated diseases often being coincidental.
  • EXT1/EXT2-associated MN was observed in younger women with active systemic autoimmunity.
  • SEMA3B-associated MN was not found; THSD7A, NELL-1, PCDH7, and NCAM-1 associated MN were rare.
  • Septuple-negative MN frequently had associated malignancy or systemic autoimmunity.

Conclusions:

  • The distinction between primary and secondary MN is insufficient for comprehensive classification.
  • A novel terminology combining target antigen and associated disease offers improved classification and clinical guidance for MN.
  • This antigen-based classification aids in understanding the diverse clinical and pathological spectrum of MN.

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