Kidney Week

Abstract: FR-OR39

NCAM1 Is an Autoantigen in Membranous Lupus Nephritis

Session Information

• Glomerular Diseases: Charting New Territory
  October 23, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Caza, Tiffany, Arkana Laboratories, Little Rock, Arkansas, United States

Tiffany Caza, MD, PhD



Dr. Tiffany Caza is a nephropathologist at Arkana Laboratories in Little Rock, Arkansas. She has a strong interest in translational research in autoimmune kidney diseases (particularly lupus nephritis), as well as immunology / serology. She is also a faculty member in the Nephrology Social Media Collective, is an avid supporter of free open-access medical education in nephrology, and enjoys teaching.

• Hassen, Samar, Arkana Laboratories, Little Rock, Arkansas, United States

Samar Hassen,

• Kuperman, Michael Benjamin, Arkana Laboratories, Little Rock, Arkansas, United States

Michael Benjamin Kuperman,

• Edmondson, Ricky, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Ricky Edmondson,

• Herzog, Christian, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Christian Herzog,

• Storey, Aaron J., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Aaron J. Storey,

• Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

John M. Arthur,

• Dvanajscak, Zeljko, Arkana Laboratories, Little Rock, Arkansas, United States

Zeljko Dvanajscak,

• Sharma, Shree G., Arkana Laboratories, Little Rock, Arkansas, United States

Shree G. Sharma,

• Kenan, Daniel J., Arkana Laboratories, Little Rock, Arkansas, United States

Daniel J. Kenan,

• Al-Rabadi, Laith, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, United States

Laith Al-Rabadi,

• Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States

Christopher Patrick Larsen,

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