Abstract
IgA nephropathy is a glomerulonephritis whose diagnosis requires biopsy-based evidence of predominant IgA1 deposits in the glomerular mesangium. In clinical terms, the condition involves marked erythrocyturia associated with mild proteinuria.
It develops as a result of increased production and subsequent deposition of circulating immune complexes into glomeruli, with the antigen being incomplete carbohydrate chains of the immune globulin A1 (IgA1) hinge regions and the antibody being IgG or IgA1 binding specifically to these carbohydrate chains. The hinge region carbohydrate chains are composed of N-acetyl galactosamine (GalNAc), linked to serine or threonine by a glycoside bond.
In healthy individuals, galactose (Gal) is linked to GalNAc (Gal). Another monocarbohydrates of the carbohydrate chain is neuraminic acid (NeuAc), linked to Gal or GalNAc, or to both of these monocarbohydrates.
Patients with IgA nephropathy lack, in some carbohydrate chains, IgA Gal, and terminal GalNAc is the antigen epitope for natural and generally occurring, circulating anti-GalNAc antibody. The formed circulating immune complexes are deposited in the glomerular mesangium.
The O-glycoside chain terminating with GalNAc is referred to as the Tn-antigen or only the T-antigen; if the chain is composed of the dissacharide GalNAc-Gal, it is referred to as the TF (Thomsen-Friedenreich) antigen. Increased Tn and TF expression has been found in a variety of tumor cells, primarily in gastrointestinal tract tumors.
Terminal GalNAc on erythrocyte, monocyte, and thrombocyte membrane glycoproteins is the cause for the rare Tn syndrome.