IgG subclass profile of serum antigliadin antibodies and antibody-dependent cell-mediated cytotoxicity in young children with coeliac disease

Abstract

Recently, sera from children with active coeliac disease were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of gliadin-coated cells. In the present study, the subclass profile of immunoglobulin (Ig)G antigliadin antibodies in sera from young children, with or without coeliac disease, was determined and related to the ADCC-mediating capacity of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untreated coeliac disease had high antigliadin antibody activities of all four IgG subclasses. However, they had a particularly high proportion of IgG1 antigliadin antibodies (ratio IgG1/IgG) compared with healthy references or coeliac children in remission. In contrast, children who had high serum antigliadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodies of the IgG1 as well as the IgG3 subclass compared with healthy references or untreated coeliac children. Regression analysis showed that IgG1 and IgG3 antigliadin antibody activity correlated positively to ADCC-mediating capacity, and depletion of IgG1 from sera profoundly diminished ADCC. The results suggest that gliadin-specific antibodies of predominantly the IgG1 subclass mediate tissue-damaging immune reactions like ADCC, and may, thus, contribute to the disease process of coeliac disease.