Galactose-deficient Immunoglobulin A1 (Gd-IgA1) (Gd-IgA1)

Galactose-deficient Immunoglobulin A1 (Gd-IgA1) is an aberrantly glycosylated form of IgA1 that serves as the central pathogenic autoantigen in IgA nephropathy (IgAN) [NIH, PMC9181435]. In patients with IgAN, the O-glycans in the hinge region of IgA1 lack terminal galactose, exposing N-acetylgalactosamine (GalNAc) residues [NIH, PMC10440440]. This structural abnormality triggers the production of anti-glycan autoantibodies, leading to the formation of large, nephritogenic immune complexes that deposit in the glomerular mesangium [Frontiers in Immunology, 2023]. These deposits activate the complement system and induce mesangial cell proliferation, inflammation, and progressive renal fibrosis [Kidney International, 2022]. Therapeutic strategies focus on reducing the circulating levels of Gd-IgA1 by targeting its production pathways, including the use of BAFF/APRIL inhibitors, plasma cell-depleting agents, and targeted-release corticosteroids that modulate mucosal immunity [NIH, PMC10440440]. Monitoring serum and urinary Gd-IgA1 levels is increasingly used for diagnosis and to assess disease activity and treatment response [Frontiers in Medicine, 2023].

Other names

Gd-IgA1Aberrantly glycosylated IgA1Under-galactosylated IgA1Hinge-region galactose-deficient IgA1O-glycosylation-deficient IgA1

Reduction of Gd-IgA1 production through inhibition of B-cell survival factors (BAFF and APRIL), depletion of IgA-secreting plasma cells via CD38 inhibition, or localized suppression of mucosal immune responses in the gut-associated lymphoid tissue (GALT).