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Dual-antigen membranous nephropathy.

Samih H Nasr1, Tiffany N Caza2, Christopher P Larsen2

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

Kidney International
|November 6, 2025
PubMed
Summary
This summary is machine-generated.

Dual antigen membranous nephropathy (MN) is likely underdiagnosed, involving various MN antigens. Liquid chromatography tandem mass spectrometry (LC MS/MS) is valuable for detecting dual antigen MN.

Keywords:
EXT1/EXT2NCAM1NELL1contactin-1mass spectrometrymembranous nephropathy

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Area of Science:

  • Nephrology
  • Immunopathology
  • Biomarker Discovery

Background:

  • Membranous nephropathy (MN) typically involves a single primary antigen.
  • Rare cases of dual antigen MN have been identified using immunohistochemistry (IHC)/immunofluorescence (IF) or serologic testing.
  • This study investigated dual antigen MN at Mayo Clinic and Arkana Laboratories.

Purpose of the Study:

  • To identify and characterize cases of dual antigen membranous nephropathy.
  • To evaluate the utility of laser capture microdissection coupled with liquid chromatography tandem mass spectrometry (LC MS/MS) for detecting multiple MN antigens in kidney biopsies.

Main Methods:

  • Analysis of kidney biopsy tissue from Mayo Clinic using laser capture microdissection and LC MS/MS to detect 12 MN antigens.
  • Confirmation of dual antigen MN cases using both LC MS/MS and IHC/IF.

Main Results:

  • Nine cases of dual antigen MN were confirmed, involving combinations of NELL1, CNTN1, NCAM1, EXT1/2, NDNF, PLA2R1, THSD7A, PCDH7.
  • Patients typically presented with nephrotic syndrome and microscopic hematuria, with a median age of 68 years.
  • Dual antigen MN accounted for 2.6% of PLA2R1-negative MN cases at Mayo Clinic.

Conclusions:

  • Dual antigen MN is likely underdiagnosed, particularly when PLA2R1 is involved, as antigen detection is not routinely performed.
  • A variety of MN antigens, including podocyte-expressed, transmembrane, and secreted types, can be involved in dual antigen MN.
  • LC MS/MS is a valuable tool for identifying dual antigen MN, aiding in understanding its pathophysiology, treatment, and clinical outcomes.