Subclass Profile of IgG Antibody Response to Gluten Differentiates Non-Celiac Gluten Sensitivity from Celiac Disease

Objective: Non-celiac wheat sensitivity (NCWS) is associated with significantly elevated levels of antibody to gluten, but how these antibodies contrast with those in celiac disease is not well-understood. We aimed to characterize the subclass distribution of the IgG antibody response to gluten and explore potential relationships with markers of disease pathology. Design: Study participants included individuals who reported symptoms in response to wheat intake and in whom celiac disease and wheat allergy were ruled out, celiac disease patients, and healthy controls. Sera were analyzed for subclass profile of IgG anti-gliadin antibody response, and potential correlations between IgG subclass and previously identified markers of innate immune activation and intestinal cell damage were examined. Multivariate principal component analysis was used to assess group clustering based on subclass data. Results. In comparison with celiac disease patients, the IgG anti-gliadin antibody response in NCWS was characterized by significantly lower levels of IgG1 and IgG3, and greater levels IgG4. Within the NCWS cohort, levels of IgG4 and IgG1 anti-gliadin antibodies correlated with circulating concentrations of intestinal fatty acid-binding protein (FABP2), a marker of intestinal epithelial cell damage. In contrast, FABP2 concentration correlated with levels of IgG3 in the celiac disease cohort. Conclusions: The data reveal significant differences in the subclass distribution of IgG anti-gliadin antibody between celiac disease and NCWS, indicating divergent mechanisms in the adaptive immune response to ingested gluten. Furthermore, the subclass-specific correlation of the anti-gliadin IgG response with FABP2 expression is suggestive of a relationship between the antibodies and intestinal pathology.