Specific Association of HLA-DR4 With Increased Prevalence and Level of Insulin Autoantibodies in First-Degree Relatives of Patients With Type I Diabetes
| Autor: | Stuart J. Brink, Luis Castaño, George S. Eisenbarth, Chester A. Alper, Richard A. Jackson, Ralph Ziegler, Z Awdeh, J. S. Soeldner |
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| Rok vydání: | 1991 |
| Předmět: |
Male
musculoskeletal diseases medicine.medical_specialty Insulin Antibodies Endocrinology Diabetes and Metabolism medicine.medical_treatment Human leukocyte antigen medicine.disease_cause Nuclear Family Autoimmunity Islets of Langerhans HLA-DR3 Antigen HLA Antigens immune system diseases Immunopathology Internal medicine Diabetes mellitus HLA-DR4 Antigen Prevalence Internal Medicine medicine Humans Family First-degree relatives skin and connective tissue diseases Autoantibodies business.industry Histocompatibility Testing Insulin Haplotype Autoantibody medicine.disease Pedigree Diabetes Mellitus Type 1 Endocrinology Female business |
| Zdroj: | Diabetes. 40:709-714 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diab.40.6.709 |
| Popis: | First-degree relatives of patients with insulin-dependent (type I) diabetes (n = 264 from 106 families) were evaluated with HLA typing and determination of competitive insulin autoantibodies (CIAAs) and islet cell autoantibodies (ICAs). The levels of CIAAs in 30 relatives exceeded our upper limit of normal (greater than or equal to 39 nU/ml), and 30 had high-titer ICAs (greater than or equal to 40 Juvenile Diabetes Foundation units [JDF U]). Eleven of the HLA-typed relatives developed diabetes during follow-up. Twenty-three percent (28 of 123) of the relatives with at least one HLA-DR4 allele were CIAA+ (CIAA greater than or equal to 39 nU/ml) versus 4% (6 of 141) among DR4- relatives (P less than 0.0001). Twenty-one of 22 of the highest CIAA values were all in the DR4+ group (DR4+ vs. DR4-, P = 0.003, Wilcoxon's rank-sum test). HLA-DR3 did not correlate with the level of CIAAs, and neither DR3 nor DR4 correlated with titer of ICAs measured in JDF U. We conclude that, in first-degree relatives of patients with type I diabetes, there is a striking association with HLA-DR4 in both the prevalence of relatives exceeding the normal CIAA range and in the level of CIAAs. These data suggest that a gene on HLA-DR4 haplotypes contributes to the level of anti-insulin autoimmunity, and we hypothesize that DR4-associated diabetes susceptibility, distinct from DR3-associated susceptibility, may be secondary to this influence. |
| Databáze: | OpenAIRE |
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