Comparative analysis of organ-specific autoantibodies and celiac disease-associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects

Abstract

OBJECTIVE - In type 1 diabetes the coexistence with other endocrine diseases and organ-specific autoantibodies has been frequently reported leading to the concept of autoimmune polyendocrine syndrome (APS). In addition, an association of type 1 diabetes with celiac disease has been described. These disorders share a similar genetic background, and first-degree relatives of type 1 diabetic patients may also be affected significantly. Screening for specific antibodies allows early diagnosis of these disorders. RESEARCH DESIGN AND METHODS - In the present cross-sectional study, we analyzed sera from 197 recent-onset type 1 diabetic patients at the time of diagnosis, 882 first-degree relatives, and sera of 150 healthy control subjects for prevalence and co-occurrence of the following antibodies (method): insulin autoantibodies (radioimmunoassay) GAD and IA-2 antibodies (radioligand assay); islet cell antibody, anti-adrenal cortex antibodies, and anti-gastric parietal cell antibodies (indirect immunofluorescence); anti-thyroglobulin and anti-thyroid peroxidase antibodies; and gliadin IgG/A and tissue-transglutaminase IgA (enzyme-linked immunosorbent assay). RESULTS - The overall frequency of gastric patietal cell antibodies and adrenal antibodies did not differ significantly among groups. In contrast, type 1 diabetes-associated antibodies and thyroid antibodies were significantly more frequent both in recent-onset type 1 diabetic patients and in the group of first-degree relatives (P < 0.05). The prevalence of gliadin IgG/IgA and transglutaminase IgA was significantly higher in the group of recent-onset type 1 diabetic patients (P < 0.05), but the difference between first-degree relatives and control subjects did not reach statistical significance. Focusing on the coexistence of antibodies, the group of recent-onset type 1 diabetic patients presented with 27.4% of the subjects testing antibody-positive-specific for two or more of the envisaged disorders (i.e., type 1 diabetes, autoimmune thyroiditis, and celiac disease) compared with 3.1% in the group of first-degree relatives and 0 of 150 in the control population (P < 0.05). CONCLUSIONS - We conclude that, in an active case-finding strategy, recent-onset type 1 diabetic patients should be routinely screened at least for concomitant autoimmune thyroid disease and additionally for celiac disease. Screening in their first-degree relatives should include at a minimum the search for thyroid autoimmunity in addition to screening for pre-type 1 diabetes.