No abstract

With regard to progression to diabetes, ICA cross-reactive with mouse pancreas, antibodies to the M(r) 64,000 islet antigen (64K), antibodies immunotrapping brain GAD activity, and IAA were analysed in 53 ICA-positive first-degree relatives of IDDM patients and 18 ICA-positive schoolchildren without a family history of diabetes. Sera from 29 (55%) relatives did not bind to mouse pancreas, whereas 24 (45%) displayed cross-species reaction. ICA titres on human and mouse pancreas were weakly correlated in the overall population (p < 0.05) but more strongly (p < 0.01) in only those subjects who displayed antibodies on tissues from both species. GAD and 64K antibodies were detected in 31% and 35% of relatives. In schoolchildren, the frequencies of cross-species reactive ICA (22%), GAD antibodies (6%), 64K antibodies (22%), and IAA (6%), were lower (p < 0.05) than in relatives. A strong correlation (p < 0.0001) was observed between GAD and 64K antibodies. GAD or 64K antibodies were strongly correlated with ICA on human pancreas (p < 0.0001) but poorly with ICA on mouse pancreas (p = 0.05). After pre-incubation of sera with brain homogenate, ICA titres were unaffected on mouse pancreas but reduced on human pancreas. ICA-positive subjects who displayed neither cross-species reactive ICA nor GAD or 64K antibodies were more frequent (p < 0.05) among schoolchildren than relatives, whereas subjects who displayed all antibody specificities were more numerous (p < 0.04) in relatives. All relatives with ICA binding only to human pancreas, as well as all schoolchildren, permanently displayed an AIRG higher than the first control percentile and remained non-diabetic.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

No abstract

We studied the heterogeneity of cytoplasmic islet-cell antibodies for cross-reaction with mouse pancreas in 31 recent-onset Type 1 (insulin-dependent) diabetic patients and 31 first-degree relatives with islet-cell autoantibodies detected on human pancreas. Only six Type 1 diabetic patients displayed islet-cell antibodies binding to human pancreas but not to mouse pancreas. Among 15 first-degree relatives displaying such antibodies which did not react with mouse pancreas, including one identical twin and one subject with polyglandular autoimmunity, none developed diabetes or even lost acute insulin response to intravenous glucose after 5 years of follow-up. By contrast, 14 of 20 (70%) of the Type 1 diabetic patients with islet-cell antibodies detected on human pancreas, and five first-degree relatives who progressed to a loss of acute insulin response to glucose and then to either Type 1 diabetes or glucose intolerance, also displayed antibodies reactive with mouse islets. Surprisingly, islet-cell antibodies were detectable on mouse pancreas but not on human pancreas in four Type 1 diabetic patients and in one relative who progressed to diabetes. In the five relatives who progressed to metabolic abnormalities, islet-cell antibody titres on mouse pancreas, quantified by the fluorescence intensity per islet at each serum dilution, progressively increased concomitantly with the loss of acute insulin response to glucose, whereas islet-cell antibody titres on human pancreas remained stable. The usefulness of such quantification was also validated by the fact that antibody titres on mouse pancreas were decreased after 3 months (p < 0.01) in recent-onset Type 1 diabetic patients, while titres on human pancreas were not.(ABSTRACT TRUNCATED AT 250 WORDS)