DISTINCT CYTOPLASMIC ISLET CELL ANTIBODIES WITH DIFFERENT RISKS FOR TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

The cytoplasmic islet cell antibody patterns of sera from islet cell a ntibody positive non-diabetic and diabetic endocrine autoimmune patien ts, and newly-diagnosed Type 1 (insulin-dependent) diabetic patients w ere characterised using four layer immunofluorescence with monoclonal anti-proinsulin or anti-glucagon antibodies. Two distinct islet cell a ntibody types were identified. One gave a diffuse cytoplasmic staining in both Beta and Alpha cells ('whole' islet pattern), and was not aff ected by pre-incubation with rat brain homogenate. The other had a gra nular appearance with staining restricted predominantly to Beta cells ('selective' islet pattern) and was completely inhibited by pre-incuba tion with rat brain homogenate. Some sera appeared to have a 'mixed' i slet pattern, in which glucagon-positive cells gave a weaker cytoplasm ic staining than proinsulin-positive cells. The granular 'selective' p attern was found in sera from 19 (79%) of 24 non-diabetic endocrine au toimmune patients, in two (22%) endocrine autoimmune patients who deve loped Type 1 diabetes (p < 0.0001 vs non-diabetic endocrine autoimmune patients), and in none of 19 newly-diagnosed diabetic patients. The ' whole' islet pattern was found only in sera from patients who had, or who subsequently progressed to, Type 1 diabetes. This study has identi fied a novel islet cell antibody specificity and demonstrates that in islet cell antibody positive endocrine autoimmune patients, only islet cell antibodies which stain both Beta and Alpha cells are associated with progression to Type 1 diabetes.