Hypogalactosylation of serum IgG in patients with coeliac disease

Abstract

Coeliac disease (CD) is described as an autoimmune enteropathy associated with the presence of IgG and IgA antigliadin and antitransglutaminase autoantibodies. While of diagnostic significance, the role of these autoantibodies in the immunopathogenesis of CD is elucidated. An inappropriate T cell immune response to gluten is also involved in the pathogenesis of CD, as evidenced by autoantibody switching. The N-glycans released from serum IgG of CD patients and three groups of healthy controls, of differing age ranges, were analysed by NH2-high performance liquid chromatography (HPLC). The fucosylated biantennary N- glycans were the most abundant neutral oligosaccharides; in particular, the agalacto form (G0F) showed a mean value of 42% (s.d. +/- 7.4), 30% (s.d. +/- 5.9), 26% (s.d. +/- 4.2) and 35% (s.d. +/- 6.8) for CD patients, healthy children, healthy adults under 40 and healthy adults over 40 years old, respectively. The ratio of asialo agalacto fucosylated biantenna to asialo monogalacto fucosylated biantenna (G0F)/(G1F) for CD patients showed a significant increase compared to healthy children (P < 0.0002), healthy adults under 40 (P < 0.0002) and healthy adults over 40 years old (P < 0.01). Hypogalactosylation was more pronounced for CD patients than for the patients with other autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis.

Fig. 1

NH2-HPLC separation of oligosaccharide pools after enzymatic deglycosylation and flourophore labelling of serum IgG from: (a) healthy child as negative control (sample 8C); (b) coeliac disease patient (sample 58P); (c) the most abundant neutral N-glycans structures of human IgG serum. MonoS: monosialylated structures.

Fig. 2

Plotting of the mathematical expression Ln(G0F/G1F) for three negative controls and coeliac disease, rheumatoid arthritis and psoriatic arthritis groups to characterize G0–IgG glycoform change in autoimmune diseases. Mean + 1·96*s.e. is the confidence interval for each group at a confidence level of 0·95. Standard errors were calculated using pooled variance. Overlapping of confidence intervals of two groups indicates that there is no significant difference between them.

Fig. 3

Comparative analysis of the oligosaccharide population as percentage of the total neutral N-glycans from serum IgG in patients of autoimmune diseases (coeliac disease, psoriatic arthritis and rheumatoid arthritis) and negative controls belonging to three different groups: children up to 12 years, adults under 40 years and adults over 40 years old. The points represent mean values, the boxes standard errors and the whiskers confidence intervals at a confidence level of 0·95. Standard errors were calculated using pooled variance.