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 with specific cellular receptors that mediate biological events. In this study, we have analyzed the detailed glycoform structure of the human serum IgA1 Fc O-glycosylated hinge region by electrospray ionization liquid mass spectrometry. The IgA1 fragments containing the hinge glycopeptide were separated from 4 IgA nephropathy patient (IgAN) pooled sera, 10 non-IgAN pooled sera with other primary glomerulonephritides, and 5 healthy control subject pooled sera by trypsin treatment and Jacalin affinity chromatography. The molecular weights of IgA1 hinge glycopeptide were estimated using mass spectrometry, 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 suggested the possibility that the decreased galactosylation and sialylation of the IgA1 hinge result in its glomerular deposition in IgAN.
Odani
H
H
Department of Internal Medicine, Nagoya University Daiko Medical Center, 1-1-20 Daiko-minami, Higashi-ku, Nagoya, 461-0047, Japan. hirokood@med.nagoya-u.ac.jp
Hiki
Y
Y
Takahashi
M
M
Nishimoto
A
A
Yasuda
Y
Y
Iwase
H
H
Shinzato
T
T
Maeda
K
K
D000328:Adult; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D005690:Galactose / Q000737:chemistry / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D005921:Glomerulonephritis / Q000097:blood; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006020:Glycopeptides / Q000737:chemistry; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000097:blood*
D006020:Glycopeptides; D007070:Immunoglobulin A; D010455:Peptides; D019158:N-Acetylneuraminic Acid; D005690:Galactose