Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since Il)DM seems to develop after a prodromal period of,8-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered (3-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDIM, whereas 1 patient progressed to a high 64,000 M, immunoreactivity, at a time where a commencement of a decline in (3-cell function was detected. 64,000 M, antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of (-cell autoimmunity and may be useful to predict a later development of IDDM.

Spontaneous insulin-dependent diabetes mellitus (IDDM) in the BB rat is associated with the presence of antibodies to a 64-kilodalton rat islet cell protein. These protein antibodies appeared in young animals and remained for as long as 8 weeks before the clinical onset of IDDM. Antibodies to a 64-kilodalton human islet cell protein were found to be associated with human IDDM. Detection of the antibodies may therefore be used to predict an early immune reaction against pancreatic B cells.

SUMMARY

LETTERS TO NATURE microtubule moves forward (Fig. 4). Rotation of the microtubules was most obvious for microtubules grown from fragments of outer doublets that had dissociated from the axonemes. The intrinsic curvature of these fragments provided an asymmetrical marker for the radial orientation of the microtubules 14 •

No abstract