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

Recently, sera from children with active coeliac disease were found to effi ciently induce antibody-dependent cell-mediated cytotoxicity (ADCC) of glia din-coated cells. In the present study, the subclass profile of immunoglobu lin (Ig)G antigliadin antibodies in sera from young children, with or witho ut coeliac disease, was determined and related to the ADCC-mediating capaci ty of the same sera. In addition, IgG subclasses were selectively depleted from sera and the effect on ADCC-mediating was studied. Children with untre ated coeliac disease had high antigliadin antibody activities of all four I gG subclasses. However, they had a particularly high proportion of IgG1 ant igliadin antibodies (ratio IgG1/IgG) compared with healthy references or co eliac children in remission. In contrast, children who had high serum antig liadin antibody activity but no histological signs of enteropathy (disease references), showed significantly lower proportions of antigliadin antibodi es of the IgG1 as well as the IgG3 subclass compared with healthy reference s or untreated coeliac children. Regression analysis showed that IgG1 and I gG3 antigliadin antibody activity correlated positively to ADCC-mediating c apacity, and depletion of IgG1 from sera profoundly diminished ADCC. The re sults suggest that gliadin-specific antibodies of predominantly the IgG1 su bclass mediate tissue-damaging immune reactions like ADCC, and may, thus, c ontribute to the disease process of coeliac disease.