β4-Galactosyltransferase Deficiency and IgA Nephropathy

Abstract

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, and about 40% of the patients progress to renal failure 20 years after the onset of the disease in Japan. IgAN is characterized by glomerular mesangial expansion and IgA deposition. However, the pathological molecular mechanisms remain to be fully elucidated. Pathological roles for the abnormal serum IgA, especially abnormal galactosylation and sialylation of O-glycans of IgA1, have been proposed. We have reported that β1,4-galactosyltransferase-I-deficient (β4GalT-I^-/-) mice spontaneously developed human IgAN-like disease with IgA deposition and expanded mesangial matrix (Nishie et al. 2007). This is the first report to demonstrate that genetic remodeling of protein glycosylation causes IgAN.