Abstract
IgA nephropathy is an autoimmune disease characterized by IgA1-containing glomerular immune deposits. We previously proposed a multi-hit pathogenesis model in which patients with IgA nephropathy have elevated levels of circulatory IgA1 with some O-glycans deficient in galactose (Gd-IgA1, autoantigen). Gd-IgA1 is recognized by anti-glycan IgG and/or IgA autoantibodies, resulting in formation of pathogenic immune complexes. Some of these immune complexes deposit in the kidney, activate mesangial cells, and incite glomerular injury leading to clinical presentation of IgA nephropathy. Several studies have demonstrated that elevated circulatory levels of either Gd-IgA1 or the corresponding autoantibodies predict progressive loss of renal clearance function. In this study we assessed a possible association between serum levels of Gd-IgA1 and IgG or IgA autoantibodies specific for Gd-IgA1 in serum samples from 135 patients with biopsy-proven IgA nephropathy, 76 patients with other renal diseases, and 106 healthy controls. Our analyses revealed a correlation between the concentrations of the autoantigen and the corresponding IgG autoantibodies in sera of patients with IgA nephropathy, but not of disease or healthy controls. Moreover, our data suggest that IgG is the predominant isotype of Gd-IgA1-specific autoantibodies in IgA nephropathy. This work highlights the importance of both initial hits in the pathogenesis of IgA nephropathy.
Highlights
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and a frequent cause of end-stage renal disease.[1]
Whereas student t-test analysis of these data identified a significant difference (P
This study identified a quantitative association between Gd-IgA1 and the corresponding GdIgA1-specific IgG autoantibodies which may suggest a causality relationship
Summary
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and a frequent cause of end-stage renal disease.[1] IgAN is diagnosed by evaluation of renal biopsy specimen and characterized by mesangial IgA deposits as the predominant or codominant immunoglobulin.[2, 3] Of the two human IgA subclasses, IgA1 and IgA2, only IgA1 is found in the glomerular deposits of patients with IgAN.[4, 5] Unlike IgA2, IgA1 has clustered O-.
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