Polyspecificity of autoimmune responses in type 1 (autoimmune) diabetes

Extract

Autoimmunity is, by definition, supposed to be antigen specific [1], yet for almost 50 years, associations have been recognized between different autoimmune diseases [2–5]. For example, the increased incidence of gastric and thyroid autoimmunity in type 1 diabetes was first reported in 1963 [6]. These associations are in addition to the occasional cases of the autoimmune polyglandular syndromes [7] and are found independently of chronic mucocutaneous moniliasis, which is characteristic of the Type I syndrome (APECED), and Addison's disease which invariably occurs in the Type II syndrome [8].

In the 1980s, Riley et al. [9] reported that about 5% of young patients with type 1 diabetes had achlorhydria (lack of gastric acid) secondary to autoimmune gastritis. About twice that number had gastric parietal cell autoantibodies, while the frequency of gastric parietal cell autoantibodies in healthy children the same age was only 2%. In a separate study, thyroid function tests of young diabetic patients revealed that about 1% had Grave's disease (autoimmune hyperthyroidism) and about 7% had Hashimoto's disease (autoimmune thyroiditis). Again, another 10% of patients tested positive for thyroid microsomal autoantibodies without concurrent evidence of clinical disease [10]. This frequency of antithyroid autoantibodies is about five times that found in healthy children of a similar age [11]. Thyroid microsomal autoantibodies were even more frequent in patients with both type 1 diabetes and autoimmune gastritis, affecting 46% of Caucasian, and 25% of black subjects [9].