Antibodies to tissue transglutaminase C in type I diabetes

Aims/hypothesis. Silent coeliac disease is a gluten driven autoimmune disease which is relatively frequent in patients with Type I (insulin-dependent) diabetes mellitus. To determine the extent of gluten associated autoimmunity in Type I diabetes, autoantibodies to tissue transglutaminase C, a major autoantigen in coeliac disease, were measured in patients with new-onset Type I diabetes. Methods. We measured IgG and IgA tissue transglutaminase C autoantibodies using human recombinant antigen and radio-binding assays in a cohort of 287 patients with new-onset Type I diabetes, 119 with Type II (non-insulin-dependent) diabetes mellitus and in 213 control subjects. Results. We found IgA and IgG tissue transglutaminase C antibodies in 24 (8%) patients with Type I diabetes; 97 (33%) patients had IgG antibodies only and 1 IgA antibodies only. Antibody concentrations were highest in those with both IgA and IgG antibodies. Only 2 (2%) patients with Type II diabetes and 2 (1%) control subjects had either IgG or IgA tissue transglutaminase C antibodies. Patients with HLA DRB1*04 alleles had the highest prevalence of IgG tissue transglutaminase C antibodies. Conclusion/Interpretation. These data show that almost 10% of patients have autoimmunity typical of coeliac disease and that another 30% have low level tissue transglutaminase C antibody binding. This high prevalence suggests either involvement of the gut in the pathogenesis of Type I diabetes or that transglutaminase is a secondary autoantigen resulting from beta-cell destruction.