Antibody cross-reactivity and the viral aetiology of type 1 diabetes

Type 1 diabetes (T1D) is caused by the destruction of insulin-producing pancreatic β cells by the patient's immune system. While the underlying genetics and immunopathology are fairly well characterized, the environmental trigger remains unidentified. Numerous studies have centred on the role of enteroviruses as aetiological factors that could initiate or accelerate T1D development. The most convincing evidence to date consists of an array of reports documenting the presence of enteroviral nucleic acids in peripheral blood at diagnosis. A prominent hypothesis is that enteroviruses may infect the pancreatic islets and thus be responsible for the islet-specific up-regulation of MHC class I that is commonly observed, possibly enabling T cell recognition and cytotoxicity. Past immunohistochemical studies have indeed shown that antibodies binding the enteroviral capsid protein VP1 preferentially stain the pancreatic β cells from diabetic individuals. New data now indicate that the VP1 antibody used in these studies cross-reacts with mitochondrial proteins.