Cytokines and Production of Aberrantly O-Glycosylated IgA1, the Main Autoantigen in IgA Nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide, with no disease-specific treatment and up to 40% of patients progressing to kidney failure. IgA nephropathy (IgAN), characterized by IgA1-containing immunodeposits in the glomeruli, is considered to be an autoimmune disease in which the kidneys are injured as innocent bystanders. Glomerular immunodeposits are thought to originate from the circulating immune complexes that contain aberrantly O-glycosylated IgA1, the main autoantigen in IgAN, bound by IgG autoantibodies. A common clinical manifestation associated with IgAN includes synpharyngitic hematuria at disease onset or during disease activity. This observation suggests a connection of disease pathogenesis with an activated mucosal immune system of the upper-respiratory and/or gastrointestinal tract and IgA1 glycosylation. In fact, some cytokines can enhance production of aberrantly O-glycosylated IgA1. This process involves abnormal cytokine signaling in IgA1-producing cells from patients with IgAN. In this article, we present our view of pathogenesis of IgAN and review how some cytokines can contribute to the disease process by enhancing production of aberrantly glycosylated IgA1. We also review current clinical trials of IgAN based on cytokine-targeting therapeutic approaches.

Citation

Taylor Person, R Glenn King, Dana V Rizk, Jan Novak, Todd J Green, Colin Reily. Cytokines and Production of Aberrantly O-Glycosylated IgA1, the Main Autoantigen in IgA Nephropathy. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2022 Jul;42(7):301-315

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PMID: 35793525

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