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| PROGNOSTICALLY SIGNIFICANT HETEROGENEITY OF CYTOPLASMIC ISLET CELL ANTIBODIES IN RELATIVES OF PATIENTS WITH TYPE-I DIABETES |
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| Author(s): GIANANI R, PUGLIESE A, BONNERWEIR S, SHIFFRIN AJ, SOELDNER JS, ERLICH H, AWDEH Z, ALPER CA, JACKSON RA, EISENBARTH GS |
| Source: DIABETES Volume: 41 Issue: 3 Pages: 347-353 Published: MAR 1992 |
| Times Cited: 140 References: 20 |
| Abstract: A significant proportion of relatives of patients with insulin-dependent (type I) diabetes with high titers of cytoplasmic islet cell autoantibodies (ICAs) do not progress to overt diabetes with up to 8 yr of follow-up. This may reflect that follow-up of such relatives has not been long enough to observe diabetes, that despite expression of identical ICAs, some relatives will not progress to diabetes; or that there is heterogeneity in what is identified as ICA. We identified a subset of ICA that was restricted in its species (not reacting with mouse islets) and cell-type reactivity within islets (beta-cell specific). Only one of eight relatives whose sera had the restricted pattern of reactivity progressed to overt diabetes, and on sequential evaluation, all but the one relative who progressed to diabetes have maintained normal first-phase insulin secretion to intravenous glucose. In contrast, by life-table analysis, 70% of relatives expressing nonrestricted ICA became diabetic within 5 yr of follow-up (1 of 8 vs. 16 of 25 diabetic at last follow-up, P < 0.02). Moreover, preliminary data suggest a significant association of the human leukocyte antigen DQB1*0602 allele of DR2 haplotypes with the restricted ICA pattern (4 of 5 DQB1*0602 restricted vs. 0 nonrestricted ICA, P = 0.006). We propose that expression of a genetically determined restricted ICA pattern confers a markedly lower risk for progression to diabetes. Our studies suggest that relatives with restricted ICA may comprise most ICA+ relatives who do not develop diabetes or abnormal first-phase insulin secretion on follow-up of > 5 yr and that expression of such autoantibodies may be associated with the "protective" DQB1*0602 allele. |
| Document Type: Article |
| Language: English |
Addresses:
1. BRIGHAM & WOMENS HOSP, JOSLIN DIABETES CTR, IMMUNOL & IMMUNOGENET SECT, 1 JOSLIN PL, BOSTON, MA 02115 USA
2. CTR BLOOD RES, BOSTON, MA USA
3. MCGILL UNIV, MONTREAL H3A 2T5, QUEBEC CANADA
4. NEW ENGLAND DEACONESS HOSP, BOSTON, MA 02215 USA
5. UNIV CALIF DAVIS, DAVIS, CA 95616 USA
6. CETUS CORP, EMERYVILLE, CA 94608 USA |
| Publisher: AMER DIABETES ASSOC, 1660 DUKE ST, ALEXANDRIA, VA 22314 |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: HQ276 |
| ISSN: 0012-1797 |
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