Quantification of human cytoplasmic islet-cell antibodies which cross-react with mouse pancreas: a follow-up study in type 1 (insulin-dependent) diabetic patients and in first-degree relatives.
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)
Saï
P
P
Laboratoire d'Immuno-Endocrinologie cellulaire et moléculaire associé INRA/ENVN, Nantes, France.
Elmansour
A
A
Audrain
M
M
Charbonnel
B
B
Bardet
S
S
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009679:Nuclear Family; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012016:Reference Values; D013997:Time Factors
D001323:Autoantibodies; D007328:Insulin; C024211:islet cell antibody