NCAM1: A Novel Autoantigen in Membranous Lupus Nephritis

ABSTRACT: Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. Unlike phospholipase A2 receptor or thrombospondin type 1 domain containing 7A-associated membranous nephropathy, where known antibodies can be detected within sera by indirect immunofluorescence and/or enzyme-linked immunosorbent assay, it is not possible to monitor disease activity in membranous lupus nephritis where the target autoantigens are mostly unknown. Determination of the target autoantigen has diagnostic significance, informs prognosis, and allows for non-invasive monitoring of disease activity in serum. We utilized mass spectrometry for antigen discovery of laser capture microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue IgG immunoprecipitation studies from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1-associated membranous neuropathy was 5.7% of cases of membranous lupus nephritis. NCAM1 co-localizes with IgG within glomerular immune deposits. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring of the disease. 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Aaron Storey  

LAB HEAD: Chris Larsen

PROVIDER: PXD021123 | Pride | 2020-10-19

REPOSITORIES: Pride