Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy.
BACKGROUND
The IgA1 molecule, which is predominantly deposited in glomeruli in IgA nephropathy (IgAN), is a unique serum glycoprotein because it has O-glycan side chains in its hinge region. Our study was conducted to investigate the O-glycan structure in the glomerular IgA1 in IgAN.


METHODS
The IgA1 was separated from 290 renal biopsy specimens of 278 IgAN patients and from four serum IgA1 samples (IgAN, 2; control, 2). The variety of O-glycan glycoform was determined by estimating the precise molecular weights of the IgA1 hinge glycopeptides using matrix-assisted laser desorption ionization time of flight mass spectrometry.


RESULTS
The peak distribution of IgA1 hinge glycopeptides clearly shifted to lesser molecular weights in both glomerular and serum IgA1 in IgAN compared with the serum IgA1 of controls. In the five major peaks of IgA1 hinge glycopeptides in each sample, the numbers of carbohydrates composing O-glycans (GalNAc, Gal, and NANA) in the deposited and serum IgA1 in IgAN patients were significantly fewer than those in the serum IgA1 in the control groups.


CONCLUSIONS
The O-glycan side chains in the hinge of the glomerular IgA1 were highly underglycosylated in IgAN. These results indicate that the decreased sialylation and galactosylation of the IgA1 hinge glycopeptides play a crucial role in its glomerular deposition in IgAN.
Hiki
Y
Y
Department of Medicine, Daiko Medical Center, Nagoya University, Nagoya, Aichi, Japan. yhiki@med.nagoya-u.ac.jp
Odani
H
H
Takahashi
M
M
Yasuda
Y
Y
Nishimoto
A
A
Iwase
H
H
Shinzato
T
T
Kobayashi
Y
Y
Maeda
K
K
D000328:Adult; D002241:Carbohydrates / Q000032:analysis; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008970:Molecular Weight; D012016:Reference Values
D002241:Carbohydrates; D006020:Glycopeptides; D007070:Immunoglobulin A