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.

Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

“… 36 They may also contribute to recruitment of various leukocytes that lead to antibody-dependent cell-mediated cytotoxicity, a process that has been previously demonstrated for antibodies to gluten. 37 However, the observed immune response to nongluten proteins, as was mentioned earlier, may be the result and a bystander marker of intestinal barrier damage and inflammation, without playing a role in the pathogenic mechanism of celiac disease.…”

Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies

“…However, although interferon-γ has been shown to increase release of the human IgG2 subclass of antibody from peripheral blood mononuclear cells, it can decrease release of the IgG1 subclass of antibody (50). The IgG1 subclass of antibody is particularly elevated in coeliac disease, where it is thought to be the primary mediator of antibody-dependent cell-mediated cytotoxicity (ADCC) (51). Thus, the patient group with high overall anti-gliadin IgG could have high interferon-γ, elevated KYN and KYN-TRP ratio, high IgG2, but low IgG1 and therefore low ADCC, with better clinical outcomes.…”

ADAMTS‐13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura

“…In recent years, several previous studies have investigated the role of biomarkers in predicting the recurrence of episodic autoimmune disease. Particularly meaningful in this respect are studies about the distribution of the specific Ig subclasses (studied also in relation to a number of autoimmune diseases such as lupus erythematodes [44], rheumatoid arthritis [45], bullous dermopathies [46], celiac disease [47], type I diabetes [48], acquired hemophilia [49], sclerosing pancreatitis, autoimmune nephropathy [50] and multiple sclerosis [51]). These studies showed how each IgG subclass seems to have a distinct biological property with different actions on complement activation and immune functions.…”