Islet cell and insulin autoantibodies in subjects at high risk for development of type 1 (insulin-dependent) diabetes mellitus: the Lyon family study

Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to insulin were conducted in a population of 479 first degree relatives of 174 Type 1 (insulin-dependent) diabetic patients. Analysis of HLA haplotypes within families illustrated the high frequency...

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Bibliographic Details
Published in:Diabetologia 1988-10, Vol.31 (10), p.741-746
Main Authors: THIVOLET, C, BEAUFRERE, B, BETUEL, H, CHATELAIN, P, DURAND, A, TOURNIAIRE, J, FRANCOIS, R
Format: Article
Language:English
Subjects:
Adolescent
Adult
Autoantibodies - analysis
Biological and medical sciences
Child
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
France
Haplotypes
HLA Antigens - analysis
Humans
Insulin Antibodies - analysis
Islets of Langerhans - immunology
Male
Medical sciences
Risk Factors
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Summary:Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to insulin were conducted in a population of 479 first degree relatives of 174 Type 1 (insulin-dependent) diabetic patients. Analysis of HLA haplotypes within families illustrated the high frequency of DR3 and DR4 alleles with preferential transmission from parent to both affected and unaffected offspring. DR4 was preferentially associated with DQw3.2 (TA10-) in 60/73 (82.2%) patients and 101/127 (79.5%) relatives. Relatives have been followed for a period of 800 subject-years. Twenty-two out of 430 relatives (5.1%) were found islet cell antibodies (ICA-IgG) positive. Seven sera with low titres became negative 6 months later at two different determinations. Fifteen sera ICA-IgG and ICA-protein A positive with high titres remained positive thereafter. Half of the ICA positive relatives were also found insulin autoantibodies (IAA) positive. All but 3 ICA negative relatives did not have IAA in their sera. Analysis of IAA specificity with competition experiments indicated that most antibodies recognised epitopes shared between human and pork insulins while four were specific for human insulin determinants. Analysis of class I and class II HLA antigen distribution indicated no particular allelic restriction in antibody positive individuals. Metabolic status of antibody positive relatives was determined with oral and intravenous charge of glucose. Two haplo-identical DR3-DQw2 brothers became diabetic during the study. One child and one mother both with DR4-DQw3.2 became intolerant to glucose. Each of these relatives had high titre ICA prior to metabolic deterioration.
ISSN:0012-186X
1432-0428
DOI:10.1007/BF00274776