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Abstract: PO1900

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

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bobart, Shane A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tehranian, Shahrzad, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Alexander, Mariam P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Vrana, Julie A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Said, Samar M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Giesen, Callen D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • De Vriese, An S., AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium
Background

Primary membranous nephropathy (MN) is caused by circulating auto-antibodies against podocyte surface antigens, identified as M-type-phospholipase–A2-receptor (PLA2R) in 70-80% and thrombospondin-type-1-domain-containing-7A (THSD7A) in 2-5% of patients. Secondary MN occurs in the context of malignancy, auto-immune disease, infection, paraproteinemia or medication. Some patients with PLA2R-associated MN have a current or previously diagnosed associated condition, but it remains unclear whether it is causally related or coincidental. A few THSD7A-associated MN cases have a strong etiologic link with active malignancy, while in others malignancy appears coincidental. Exostosin 1/exostosin 2 (EXT1/EXT2) are recently discovered target antigens in patients with MN, the majority of whom have auto-immune disease. These recent findings blur the traditional distinction between primary and secondary MN.

Methods

To describe the phenotypes of PLA2R-, THSD7A- and EXT1/EXT2-associated MN, 201 adult patients with biopsy-proven MN were classified using serology, immunostaining and mass spectrometry. Clinical, biochemical and follow-up data were examined for associated disease and its relationship with MN.

Results

PLA2R-associated MN (n=161) occurred predominantly in middle-aged white males, with 72% presenting without associated disease. Only 1 case of THSD7A-associated MN was identified, with a concomitant malignancy. EXT1/EXT2-associated MN (n=8) was identified in younger females and was strongly linked with active auto-immunity. The majority of patients who were negative for all three target antigens (n=27/31, 87%) presented with associated disease, mainly malignancy and auto-immunity.

Conclusion

In conclusion, the historical primary-secondary dichotomy has substantial limitations when applied to MN. We propose a terminology combining the target antigen involved in pathogenesis and the associated clinical diseases in order to classify MN and guide clinical decision making.

Funding

  • Private Foundation Support