Glycosyltransferases Involved in the Biosynthesis of IgA O-Glycans
IgA nephropathy (IgAN) is a chronic inflammatory renal disease caused by the deposition of IgA1 subclass in the glomerular mesangium area, and one-third patients with IgAN could progress to end-stage renal failure. It is proposed that IgA molecules from patients with IgAN have incomplete carbohydrate chains in the O-glycan structure at the hinge region of IgA, though there is no clear evidence for this proposal. The sialyl-T (ST) antigen is a O-glycan having the following simple structure: SAα2,3Galβ1,3GalNAcα-Ser/Thr. IgA1 subclass bears at least five ST antigen in the hinge regions. It has been reported that the IgA1 molecule from the patients lacks a galactose or sialic acid residue at the end of the ST structure. The incomplete synthesis of O-glycans may induce physical change in the IgA molecule, which in turn makes IgA easy to deposit in the renal glomeruli. However, we found that only about 1% of IgA obtained from the patients contained incomplete carbohydrate chains in its molecule. Definitive diagnosis of IgAN is now being done by a renal biopsy, which imposes burden on the patients. Thus, it is required to develop novel methods for the diagnosis. Identification of glycosyltransferases involved in the biosynthesis of IgA O-glycan may lead us to elucidate cause of the disease and development of the diagnosis and therapeutic method.
KeywordsSialic Acid Renal Biopsy Hinge Region Sialic Acid Residue Renal Glomerulus
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