What Genetics Tells Us About the Pathogenesis of IgA Nephropathy: The Role of Immune Factors and Infection

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, which is characterized by IgA1-containing immune-deposits in the glomerular mesangium. The epidemiologic observations of familial clustering as well as ethnic and regional discrepancies indicate a genetic component to IgAN. Large, international, genome-wide association studies have identified several susceptibility genes and loci for IgAN, many of which have been implicated in immune regulation and are shared with other autoimmune diseases. Notably, increasing numbers of genes involved in mucosal immunity have been detected; such genes may impact the susceptibility and progression of IgAN through interaction with environmental stimuli (especially infection). Here, we discuss the innate and adaptive immune mechanisms that drive protective immunity against pathogens. Our goal is to provide a representative overview of the synergistic roles between genetic predisposition and infection in IgAN pathogenesis. We anticipate that these results will provide potential therapeutic agents and advances in precision medicine.