ISSN:
1432-0428
Schlagwort(e):
Type 1 (insulin-dependent) diabetes mellitus
;
subjects at risk
;
cytoplasmic islet-cell autoantibodies
;
mouse pancreas
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary We studied the heterogeneity of cytoplasmic isletcell 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. Our results confirm that the use of mouse pancreas, combined with the conventional assay on humanpancreas, reveals the heterogeneity of islet-cell autoantibodies. The presence of cross-species reactive islet-cell autoantibodies in subjects at risk may improve the predictive value, indicating relatives at lower risk whose antibodies are unable to bind to mouse islets. It could also allow the identification of subjects who progress to the disease without ever displaying islet-cell autoantibodies detectable on human pancreas. The increase of antibody titres on mouse pancreas during subject follow-up could be indicative of the worsening of the course during the prediabetic phase. Finally, islet-cell autoantibodies detected on mouse pancreas may be more transient after the onset of diabetes than is the more complex mixture of antibodies detected on human tissue.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00401151
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