Deciphering the Genetic Code of Autoimmune Kidney Diseases

Abstract

Autoimmune kidney diseases occur due to the loss of tolerance to self-antigens, resulting in inflammation and pathological damage to the kidneys. This review focuses on the known genetic associations of the major autoimmune kidney diseases that result in the development of glomerulonephritis: lupus nephritis (LN), anti-neutrophil cytoplasmic associated vasculitis (AAV), anti-glomerular basement disease (also known as Goodpasture’s disease), IgA nephropathy (IgAN), and membranous nephritis (MN). Genetic associations with an increased risk of disease are not only associated with polymorphisms in the human leukocyte antigen (HLA) II region, which governs underlying processes in the development of autoimmunity, but are also associated with genes regulating inflammation, such as NFkB, IRF4, and FC γ receptors (FCGR). Critical genome-wide association studies are discussed both to reveal similarities in gene polymorphisms between autoimmune kidney diseases and to explicate differential risks in different ethnicities. Lastly, we review the role of neutrophil extracellular traps, critical inducers of inflammation in LN, AAV, and anti-GBM disease, where inefficient clearance due to polymorphisms in DNase I and genes that regulate neutrophil extracellular trap production are associated with autoimmune kidney diseases.