Immune abnormalities in IgA nephropathy

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and it is characterized by mesangial IgA deposition. Asymptomatic hematuria with various degrees of proteinuria is the most common clinical presentation and up to 20%-40% of patients develop end-stage kidney disease within 20 years after disease onset. The pathogenesis of IgAN involves four sequential processes known as the four-hit hypothesis which starts with the production of a galactose-deficient IgA1 (gd-IgA1), followed by the formation of anti-gd-IgA1 IgG or IgA1 autoantibodies and immune complexes that ultimately deposit in the glomerular mesangium, leading to inflammation and injury. Although several key questions about the production of gd-IgA1 and the formation of anti-gd-IgA1 antibodies remain unanswered, a growing body of evidence is shedding light on the innate and adaptive immune mechanisms involved in this complex pathogenic process. Herein, we will focus on these mechanisms that, along with genetic and environmental factors, are thought to play a key role in disease pathogenesis. Lay Summary Immunoglobulin A (IgA) nephropathy (IgAN) is a kidney disease caused by the deposition of antibodies (IgA) in the glomerulus, the filtering portion of the kidney. As a result, filtering properties of the kidneys are lost and larger molecules like proteins cross from the blood into the urine. Up to 20%-40% of patients develop end-stage kidney disease (requiring dialysis or transplant) within 20 years after disease onset. New treatment options have become available over the last few years. This paper reviews the IgAN immune abnormalities that are targeted by the new therapies.

Automated summary

Immunoglobulin A (IgA) nephropathy (IgAN) is a common kidney disease characterized by the deposition of IgA antibodies in the glomerulus. This leads to kidney damage and can progress to end-stage kidney disease. The disease involves a complex immune process and is influenced by genetic and environmental factors.