O-linked oligosaccharides of the IgA1 hinge region: roles of its aberrant structure in the occurrence and/or progression of IgA nephropathy

Primary IgA nephropathy (IgAN) has been regarded as an immune complex-mediated glomerulonephritis characterized immunohistologically by the predominant deposition of IgA in the glomerular mesangial area with a variety of histopathologic injuries (Clarkson et al. in Ann Rev Med 38:157–168, 1987). In 1992, the characteristic structure of O-linked oligosaccharides (O-glycans) in the IgA1 hinge and its possible aberrancy were simultaneously and independently proposed by Mesteckey et al. (Cont Nephrol 104:172–182, 1993), and our group (Cont Nephrol 104:217, 1993) at the International Congress of Nephrology (IgA Nephropathy 25th year) held in Nancy, France. Since then, the aberrancy has been confirmed by several research groups and is suspected to play a role in the occurrence and/or the progression of IgAN. At the end of the 1980s, I took an interest in the existence of O-glycans in the hinge region of IgA1 and have pursued the structure of the carbohydrate chains. Since an excellent review on the structure and the role of the carbohydrate in IgA molecules was recently published by Narita et al. (Clin Ex Nephrol 12:332–338, 2008), this review focuses on the process by which I developed the idea of aberrant O-glycosylation in IgA1 molecules in IgAN patients and summarizes our recent observations concerning IgA1 molecules.