In NOD mice, endogenous retroviruses including intracisternal type A particles (IAP) are expressed in the pancreatic beta cells. Furthermore, in these mice,
insulin autoantibodies (IAA) cross-react with retroviral
protein p73 (the IAP
gag gene product), suggesting molecular mimicry between
insulin and p73. We therefore investigated whether IAA and
insulin antibodies (IA) associated with human
IDDM cross-reacted with p73. Fifty IAA positive sera from 30 newly diagnosed
IDDM before
insulin therapy and 20 non-diabetic first degree relatives of
IDDM and 27 IA positive sera from
insulin treated
IDDM, initially defined as IAA or IA positive by radioimmunoassay, were evaluated. Binding to
insulin and to p73 of these sera were analysed by ELISA. Approximately 65% of sera which bound
insulin by ELISA also bound p73. Only one sample negative for
insulin binding was positive for p73 binding. Preabsorption with either
insulin or p73 inhibited binding to both
insulin and p73. However, preabsorption with mouse
hemoglobin had no effect on their binding. Repeat measurement of binding to
insulin and p73 in 10 non-diabetic first degree relatives of
IDDM over an average of 16.6 months showed that each individual's reactivity to
insulin and to p73 was relatively stable over time. Furthermore, in different individuals, binding to p73 and to
insulin was closely correlated over time. In addition, 75 healthy teenagers (IAA negative by RIA) were used as normal controls in this study. p73 binding was found in only two (2.7%) of the 75 subjects. These results indicate that approximately 65% of ELISA (+) IAA and IA subjects have
antibodies which recognize both
insulin and p73, suggesting that IAA and IA from some subjects recognize an
epitope shared between human
insulin and the murine
gag gene product. This raises the possibility that for some subjects who are IAA positive, the immunizing
antigen may be antigenically similar to p73, rather than
insulin, and that endogenous retroviruses may be involved in human
IDDM.