Anti-islet autoantibodies detected by monoclonal antibody 1A2: further studies suggesting a role in the pathogenesis of IDDM

Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87 % of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3–19 %). Sera from 41.9 % of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6 % of parents and 37.9 % of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85 %) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2. [Diabetologia (1996) 39: 1365–1371]