Quantitation of saccharide compositions of O-glycans by mass spectrometry of glycopeptides and its application to rheumatoid arthritis.
Profiling of oligosaccharide structures is widely utilized for both identification and evaluation of glycobiomarkers, and site-specific profiling of N-linked glycans of glycoproteins is conducted by mass spectrometry of glycopeptides. However, our knowledge of mucin-type O-glycans including site occupancy and profile variance, as well as attachment sites, is quite limited. Saccharide compositions and site-occupancy of O-glycans were calculated from the signal intensity of glycopeptide ions in the mass spectra and tandem mass spectra from electron transfer dissociation. The results for two major plasma glycoproteins, IgA1 and hemopexin, representing clustered and scattered O-glycan attachments, respectively, indicated that the variability in modifications among individuals is so small as to justify rigorous standards enabling reliable detection of disease-related alterations. Indeed, this method revealed a novel abnormality associated with rheumatoid arthritis: a significant decrease in the N-acetylgalactosamine content of IgA1 O-glycans, indicating that the glycosylation abnormality is not limited to hypogalactosylation of IgG N-glycans in chronic inflammatory conditions.
Wada
Yoshinao
Y
Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho Izumi, Osaka 594-1101, Japan. waday@mch.pref.osaka.jp
Tajiri
Michiko
M
Ohshima
Shiro
S
D000116:Acetylgalactosamine / Q000737:chemistry; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry*; D006466:Hemopexin / Q000737:chemistry; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D009077:Mucins / Q000737:chemistry; D009844:Oligosaccharides / Q000032:analysis*; D011134:Polysaccharides / Q000032:analysis*
D006020:Glycopeptides; D007070:Immunoglobulin A; D009077:Mucins; D009844:Oligosaccharides; D011134:Polysaccharides; D006466:Hemopexin; D000116:Acetylgalactosamine