Abnormal immunoregulation in patients with insulin dependent diabetes mellitus and their healthy first degree relatives

Autoantibodies, cell-mediated autoimmunity, and impaired suppressor T cell function, suggesting abnormal immunoregulation, have been implicated in the pathogenesis of juvenile-onset insulin dependent diabetes mellitus (IDDM). To examine one of the parameters of immunoregulation, and to explore its relationship to the disease, we tested suppressor cell function in IDDM patients, their clinically healthy relatives, and in normal unrelated controls. 9/15 IDDM had impaired suppressor cell function compared to 1/8 age-matched healthy sibs (p less than 0.04) and to 0/9 unrelated controls (p less than 0.005). There was no correlation between abnormal suppressor cell function and the patient's age, sex, preprandial blood glucose levels, age at the time of diagnosis, or duration of the disease. However, there was a trend for a higher proportion of HLA Dr3 positive diabetics to have abnormal suppressor cell function compared to DR3 negative patients. Impaired suppressor cell function was also found in 5/23 clinically healthy first degree relatives; 4/5 were related to a diabetic who demonstrated abnormal suppressor cell function. These findings raise the possibility that underlying familial, probably genetically determined abnormalities in immunoregulation, acting in concert with other environmental or genetic factors, may contribute to disease susceptibility in IDDM.