IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of kidney
failure. It is a mesangioproliferative glomerular disease defined by characteristic IgA1 mesangial deposits.
These mesangial deposits likely originate from circulating immune complexes that contain IgA1 with Galactose
(Gal)-deficient O-glycans (Gd-IgA1) that are bound by IgG autoantibodies. The pathogenesis model describing
IgAN as an autoimmune disease was based on the discovery of IgG autoantibodies that bind Gd-IgA1 in the
laboratory of Dr. Jan Novak at the University of Alabama at Birmingham (UAB). As part of these studies, Dr.
Novak's laboratory developed assays for the detection and quantitative assessment of both Gd-IgA1 and IgG
autoantibodies. The use of these assays for analysis of serum samples from several cohorts of IgAN patients
has been published; both the Gd-IgA1 assay and the IgG autoantibody assay have potential as markers for
preclinical detection of IgAN, prediction of outcome, and monitoring the response to therapy. The established
pathogenesis model of IgAN enabled pharmaceutical industry to start developing and testing treatment for the
disease. However, only secondary markers (e.g., proteinuria and estimated glomerular filtration rate [eGFR])
are currently used as the endpoints, adding to the time and cost of clinical trials. Thus, clinical-grade tests that
assess primary causative markers are urgently needed. To address this requisite, we have licensed the
intellectual property from UAB that surrounds the IgAN assays developed in Dr. Novak's laboratory. The goal
of this proposal is to characterize and validate the components of the IgG autoantibody assay and establish
standard operating procedures (SOPs) so that it can be validated and commercialized for clinical use.