β-Cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Gylling, Mikhail and Tuomi, Tiinamaija and Bjorses, Petra and Kontiainen, Sirkka and Partanen, Jukka and Christie, Michael R. and Knip, Mikael and Perheentupa, Jaakko and Miettinen, Aaro (2000) β-Cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Journal of Clinical Endocrinology and Metabolism, 85 (12). pp. 4434-4440. ISSN 0021-972X

Full content URL: http://press.endocrine.org/doi/full/10.1210/jcem.8...

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β-Cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

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Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the auto-immune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. Autoantibodies against the IA-2 tyrosine phosphatase-like protein (IA-2 ab) or insulin (IAA) have been suggested to be better markers for active β-cell destruction. We studied these antibodies in sera from 60 Finnish patients with APECED, 12 of whom subsequently developed type 1 diabetes. Four (36) of the 11 patients for whom we had prediabetic samples had IA-2 ab, and 4 (36%) had IAA. None of the 48 nondiabetics had IAA, and only 2 (4%) had IA-2 ab. Both had the antibodies for years without diabetes. Thus, IA-2 ab or IAA have a low sensitivity (36%), but high specificity (96% or 100%), with a positive predictive value of 67% for type 1 diabetes in patients with APECED. Data for human leukocyte antigen haplotypes were available for 59 of the patients, including 11 diabetics, and for 8 additional nondiabetic Finnish patients. No association between type 1 diabetes and high risk genotypes was seen. None of the 11 patients with type 1 diabetes, but 15 of the 56 (27%; P < 0.05) nondiabetic patients and 24 of 93 (26%; P < 0.05) of the control subjects had the DQBi*0602 allele, which is considered protective for type 1 diabetes. This is remarkable, as previously no positive or negative associations have been reported for any disease components of APECED with human leukocyte II antigens.

Additional Information:First Published Online: July 01, 2013
Keywords:autoantibody, HLA antigen class 2, Ia antibody, insulin antibody, pancreas islet cell antibody, glutamate decarboxylase, glutamate decarboxylase 65, insulin, isoenzyme, adolescent, adult, antibody detection, article, autoimmune disease, candidiasis, child, controlled study, diagnostic value, ectodermal dysplasia, female, human, insulin dependent diabetes mellitus, major clinical study, male, priority journal, allele, autoimmune polyendocrinopathy, clinical trial, gene, genetics, glucose tolerance test, haplotype, immunology, middle aged, pancreas islet, preschool child, Adolescent, Alleles, Autoantibodies, Child, Preschool, Diabetes Mellitus, Type 1, Genes, MHC Class II, Haplotypes, Humans, Islets of Langerhans, Isoenzymes, Polyendocrinopathies, Autoimmune
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18138
Deposited On:07 Aug 2015 11:19

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