Title : Mass spectrometric determination of
IgG subclass-specific glycosylation profiles in siblings discordant for myositis syndromes
Abstract :
- Many autoimmune conditions are believed to result from chronic inflammation as a consequence of the interaction of genetic and environmental factors in susceptible individuals
- One common feature in some autoimmune diseases is the decrease in terminal galactosylation of the constant region N-glycan of the total plasma immunoglobulin
- To determine whether a similar pattern is characteristic for the autoimmune disorder myositis, we analyzed the antibody subclass specific glycosylation in patients with myositis, their asymptomatic siblings, and healthy unrelated age- and sex-matched controls
- The antibody subclass specific glycosylation was determined from the LC-MS analyses of the IgG glycopeptides generated by trypsin digestion of the antibody heavy chain
- The glycosylation profiles of the IgG subclasses were determined relative to the total abundance of all glycoforms.
- We found elevated amounts of glycoforms lacking terminal galactose in myositis patients
- Pairwise statistical analyses reveals that galactosylation is statistically different between the myositis patients and control groups
- Furthermore, the trend analysis for glycosylation indicates a pattern of decreasing galactosylation in the order controls ≥ siblings ≥ myositis patients, suggesting the existence of a genetic, immune-related predis position in the group of asymptomatic siblings that can be detected before the onset of clinical symptoms at the level of plasma proteins