Search

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.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy. [ABSTRACT FROM AUTHOR]