Aberrant Glycosylation of IgAI and Anti-Glycan Antibodies in IgA Nephropathy: Role of Mucosai Immune System

摘要

IgA nephropathy (IgAN), the most common glomerulo-nephritis, is characterized by mesangial IgAI-containing immunodeposits, proliferation of mesangial cells, and matrix expansion. Clinical onset is frequently heralded by synpharyngitic hematuria, macroscopic hematuria during an upper-respiratory tract infection. Clinical and laboratory data support a postulated extrarenal origin of the glomerular IgAI, likely derived from circulating immune complexes containing polymeric IgAI, deficient in galactose in the hinge-region O-glycans, bound by antiglycan antibodies. This aberrant IgAI is produced by IgAI-secreting cells with abnormal activities of specific glycosyltransferases. The galactose deficiency affects IgAI induced by mucosal antigens and elevated circulating levels of this abnormal IgAI are hereditable, suggesting interactions of genetic and environmental factors.