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ISLET CELL ANTIBODIES

In first-degree relatives of probands with insulin-dependent diabetes mellitus the presence of tall titre ICA of the IgG cytoplasmic variety (IgG -ICA) and ICA of the complement-fixing subgroup (CF-ICA) confer a relative risk of 75 for development of insulin-dependent diabetes mellitus. The presence of ICA combined with a decrease in the first-phase of insulin secretion ( smaller than 25 micro U/mL) is predictive with a 95% likelihood of the development of insulin-dependent diabetes mellitus within 12 months. Reproducible results among laboratories are possible with careful attention to selection of the human pancreas as substrate as well as to the use of dilutions to generate standard curves and to the transformation of results to units. The prozone phenomena described elsewhere are not general in our experience. Fifty percent of relatives with a single positive ICA test will develop insulin-dependent diabetes mellitus within 10 years, and 60-80% of relatives with both ICA and insulin autoantibodies (IAA) will develop insulin-dependent diabetes mellitus within 10 years. The predictive value for health of negative results for ICA and IAA is nearly 99%. Strong, persistently positive ICA (i.e., 40 JDF U or greater), especially if accompanied by markedly decreased insulin secretion, are the excellent predictors of subsequent development of insulin-dependent diabetes mellitus. The 64 kD beta-cell autoantigen long thought to be an significant target for ICA is not yet accessible from expression cloning despite efforts by different groups.13 ICA positivity correlates with rapid loss of C-peptide secretory ability in newly diagnosed ICA-positive insulin-dependent diabetes mellitus. The predictive values of ICA for development of insulin-dependent diabetes mellitus within 10 years in first-degree relatives of patients with insulin-dependent diabetes mellitus magnify from 40% at low levels of ICA to 100% at tall levels, whereas the sensitivity is 88% at low levels and 31% at tall levels. In common, the risk of insulin-dependent diabetes mellitus in relatives of probands increases with titre of ICA, is greater in multiplex families, and is heighten in those smaller than 10 years of age with positive ICA. Although the prevalence of ICA in Japanese with autoimmune thyroid malady resembles that in Caucasians, the incidence of insulin-dependent diabetes mellitus in the Japanese population is only 1/30 - 1/50 that in Caucasians. Prediabetics positive for ICA and IAA have heighten suppressor-inducer (CD45R) and decreased helper-inducer (CDw29) peripheral blood lymphocytes. In two randomised, prospective, placebo-controlled research of recent-onset insulin-dependent diabetes mellitus, cyclosporine immunosuppression heighten the course of non-insulin-requiring remissions as well as beta-cell function during drug treatment. Although 12 months of cyclosporine therapy decreases titres of ICA and insulin antibodies (IA) and increases glucagon-stimulated levels of serum C-peptide, the determination of ICA and IA and HLA-DR type are of no predictive value in selecting recent- onset insulin-dependent diabetes mellitus. Patients for cyclosporine immunointervention. Genetic control of autoimmunity in insulin-dependent diabetes mellitus is reviewed. EIA for autoantibodies to a 64 kD islet-cell protein is promising for prediction of insulin-dependent diabetes mellitus, but sensitivity and specificity are still suboptimal. See also: insulin antibodies.
secondary X zone   second cranial nerve   second cuneiform bone   second degree A-V block   second degree burn   second finger   second gas effect   second growth   (0)
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