Direct evidence for decreased sialylation and galactosylation of human serum IgA1 Fc O-glycosylated hinge peptides in IgA nephropathy by mass spectrometry

Human serum immunoglobulin IgA1 is produced in bone marrow and interacts wi th specific cellular receptors that mediate biological events. In this stud y, we have analyzed the detailed glycoform structure of the human serum IgA 1 Fc O-glycosylated hinge region by electrospray ionization liquid mass spe ctrometry, The IgA1 fragments containing the hinge glycopeptide were separa ted from 4 IgA nephropathy patient (IgAN) pooled sera, 10 non-IgAN pooled s era with other primary glomerulonephritides, and 5 healthy control subject pooled sera by trypsin treatment and Jacalin affinity chromatography. The m olecular weights of IgA1 hinge glycopeptide were estimated using mass spect rometry, and 13 sialo and 8 asialo glycopeptide groups were identified. The results obtained clearly showed a decrease of GalNAc, Gal, and sialic acid in IgAN compared with non-IgAN and normal controls, and those strongly sug gested the possibility that the decreased galactosylation and sialylation o f the IgA1 hinge result in its glomerular deposition in IgAN. (C) 2000 Acad emic Press.