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Islet cell autoantibodies: a family story

The islet cell autoantibody family continues to expand. When autoantibodies directed against islet cell constituents were identified by immunofluorescent staining in 1974 it opened a new world to the investigator, especially when it was recognized that islet cell autoantibodies (ICA) present in 70–80% of newly diagnosed patients were also present in some 5% of their first-degree relatives. Family studies showed that the great majority of future cases of the disease would derive from this subgroup (1). Insulin (2) and proinsulin (3) were the next autoantigens to be recognized; to date, these are the only beta cell-specific antigens to have been identified. Insulin autoantibodies (IAA) contribute little or nothing to the ICA staining pattern, but major components of this—antibodies directed against glutamatic acid decarboxylase (4) and the tyrosine phosphatase-like proteins IA-2 and IA-2 beta (5)—have been identified recently. Both types of antigen are capable of blocking the ICA staining reaction, but