Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.

Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

To document the incidence of IDDM in the Province of Turin (Italy) in the 8‐year period 1984–91 in children (0–14 years) and young adults (15–29 years), in relation to age, sex, monthly‐seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture–recapture method (99 % in childhood and 95 % in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age‐specific incidence rates were 8.42/100000 (95 % CI 7.37–9.62) and 6.72/100000 (95 % CI 5.96–7.58), respectively, in the age groups 0–14 and 15–29 years. Sex differences were evident in young adults, with an almost 1.5‐fold increased risk in men (8.37/100000, 95 % CI 7.21–9.71 vs 5.00/100000, CI 4.09–6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age‐groups with respect to glycaemia, glycosuria, ketonuria, and fasting C‐peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55 % of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984–91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups. © 1997 John Wiley & Sons, Ltd.