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Abstract: FR-OR39

NCAM1 Is an Autoantigen in Membranous Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States
  • Hassen, Samar, Arkana Laboratories, Little Rock, Arkansas, United States
  • Kuperman, Michael Benjamin, Arkana Laboratories, Little Rock, Arkansas, United States
  • Edmondson, Ricky, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Herzog, Christian, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Storey, Aaron J., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Dvanajscak, Zeljko, Arkana Laboratories, Little Rock, Arkansas, United States
  • Sharma, Shree G., Arkana Laboratories, Little Rock, Arkansas, United States
  • Kenan, Daniel J., Arkana Laboratories, Little Rock, Arkansas, United States
  • Al-Rabadi, Laith, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States
  • Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
Background

Membranous lupus nephritis is a frequent cause of proteinuria in patients with systemic lupus erythematosus. In patients with membranous lupus nephritis, the target autoantigens are largely unknown. Determination of a target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. We utilized mass spectrometry to identify target autoantigens in membranous lupus nephritis and report neural cell adhesion molecule-1 (NCAM1) as a novel target podocyte antigen.

Methods

We utilized mass spectrometry for antigen discovery of laser capture microdissected (LCMD) glomeruli and protein G immunoprecipitation studies to interrogate immune complexes. Confocal microscopy was used to examine co-localization with IgG within glomerular immune deposits. Case series of biopsies from PLA2R-negative membranous nephropathy patients (n=101) and patients with membranous lupus nephritis (n=212) were used to determine the overall frequency of these antigens. Western blotting reacting patient sera against recombinant NCAM1 protein was used to detect circulating anti-NCAM1 antibodies.

Results

NCAM1 was uniquely identified in a subset of patients with membranous lupus nephritis in LCMD glomeruli and protein G immunoprecipitations by mass spectrometry. NCAM1 co-localized with IgG within glomerular immune deposits. The prevalence of NCAM1 positivity by immunofluorescence was 6.1% of cases of membranous lupus nephritis and 2.0% of idiopathic membranous nephropathy cases. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein, demonstrating the presence of circulating antibodies.

Conclusion

We propose that NCAM1, a cytoskeleton-linked transmembrane protein, is a target autoantigen in a subset of patients with membranous lupus nephritis and within rare cases of idiopathic membranous nephropathy. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring.

Funding

  • Other NIH Support