Diabetes, Vol 45, Issue 10 1344-1349, Copyright © 1996 by American Diabetes Association

ARTICLES

Autoantibodies to protein tyrosine phosphatase-like proteins in type I diabetes. Overlapping specificities to phogrin and ICA512/IA-2

E Kawasaki, GS Eisenbarth, C Wasmeier and JC Hutton
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA.

An insulin granule membrane protein, phogrin (phosphatase homologue of granules from rat insulinoma), with homology to islet cell antigen (ICA) 512/IA-2 has recently been cloned from an insulinoma cDNA expression library with antigranule membrane sera. We have developed a radioimmunoassay for detecting antiphogrin autoantibodies using in vitro transcribed and translated phogrin and have established the sensitivity and specificity of this assay. Thirty-two of 57 (56%) new-onset patients with type I diabetes and 26 of 44 (59%) first-degree relatives followed to diabetes had anti-phogrin antibody levels exceeding the 99th percentile of 108 normal control subjects. Levels of antiphogrin autoantibodies correlated with ICA512/IA-2 autoantibodies (r = 0.82, P < 0.0001), but minimally with insulin autoantibodies (r = 0.20, P = 0.05) and not with GAD65 autoantibodies (r = 0.16, P = 0.12). Ninety-eight percent (57 of 58) of patients positive for anti-phogrin autoantibodies were also positive for autoantibodies against ICA512/IA-2. Nine percent (9 of 101) of new-onset patients and relatives followed to diabetes were ICA512/IA-2 autoantibody-positive but anti-phogrin autoantibody-negative. Preincubation of sera with recombinant ICA512/IA-2 protein completely for the majority and partially for a minority inhibited binding to in vitro translated phogrin. In three relatives in which ICA512/IA-2 autoantibodies converted to positivity with sequential follow-up, anti-phogrin autoantibodies developed at the same time. These results suggest that anti-phogrin and ICA512/IA-2 autoantibodies are related subsets of anti-islet autoantibodies.
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