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  • Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.

Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.

Kidney international (2020-10-13)
Tiffany N Caza, Samar I Hassen, Michael Kuperman, Shree G Sharma, Zeljko Dvanajscak, John Arthur, Rick Edmondson, Aaron Storey, Christian Herzog, Daniel J Kenan, Christopher P Larsen, Tiffany N Caza, Samar I Hassen, Michael Kuperman, Shree G Sharma, Zeljko Dvanajscak, John Arthur, Rick Edmondson, Aaron Storey, Christian Herzog, Daniel J Kenan, Christopher P Larsen
ABSTRACT

Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous nephropathy that known antibodies can be detected within sera, determination of the target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue protein G immunoprecipitation studies to interrogate immune complexes from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in some cases of membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1 association was 6.6% of cases of membranous lupus nephritis and in 2.0% of primary membranous nephropathy cases. NCAM1 was found to colocalize with IgG within glomerular immune deposits by confocal microscopy. Additionally, serum from patients with NCAM1-associated membranous nephropathy showed reactivity to NCAM1 recombinant protein on Western blotting and by indirect immunofluorescence assay, demonstrating the presence of circulating antibodies. Thus, we propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-NCAM1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-THSD7A antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL3779, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-PLA2R1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution