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,
E. RUSSO,
L. ZHOU,
M. A. LIPES and
G. S. EISENBARTH
Joslin Diabetes Center, Harvard Medical School, Brigham and Women's Hospital, New England Deaconess Hospital Boston, Massachusetts 02215
Using serum from a prediabetic patient as a probe, we screened 0.5 x 106 recombinants from a rat islet 
gt11 expression library. One plaque-producing antigen reactive with this prediabetic serum was identified, subcloned, and sequenced. Analysis of the sequence reveals that the clone encodes a 136-amino acid fragment of carboxypeptidase-H (enkephalin convertase). Carboxypeptidase-H is a molecule expressed within islet secretory granules and neurendocrine cells. The patient whose antibodies recognize this recombinant molecule (termed DG-1) was negative for anti-DG-1 antibodies in 1984, developed the antibodies by 1986, and remained positive until the development of diabetes in 1988. To date, serum from 5 of 20 cytoplasmic islet cell antibody-positive relatives reacted with the expressed protein, while none of 14 control sera reacted. On Western blotting, the initial patient's serum used for the screening reacts with a 52-kDa antigen corresponding to the mol wt of the membrane form of carboxypeptidase-N. The current study has identified carboxypeptidase-H as an autoantigen recognized by serum of pretype I diabetes, and the methodology used should aid in identification of additional autoantigens associated with type I diabetes.
* This work was supported by a grant from the NIH (DK-32083–09), the Eleanor Dana Charitable Trust, the Juvenile Diabetes Foundation and the Spanish Ministry of Education (to L.C.), the American Diabetes Association (to M.A.L.), and a Fullbright fellowship (to E.R.). The Joslin NIH Diabetes and Endocrinology Research Center (DK–36836) including Molecular Biology Core and Clinical Research Core was essential for these studies.
To whom requests for reprints should be addressed.
Received October 5, 1990.
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