HLA genes associated with autoimmunity and progression to disease in type 1 diabetes
- Author(s)
- Tait, BD; Colman, PG; Morahan, G; Marchinovska, L; Dore, E; Gellert, S; Honeyman, MC; Stephen, K; Loth, A;
- Details
- Publication Year 2003-02-01,Volume 61,Issue #2,Page 146-153
- Journal Title
- TISSUE ANTIGENS
- Publication Type
- Journal Article
- Abstract
- Insulin dependent diabetes mellitus (type I DM) is caused by an autoimmune process which culminates in destruction of pancreatic beta cells with resultant loss of insulin production. Preceding the clinical diagnosis of type I DM is a preclinical stage characterized by autoantibodies to insulin, glutamic acid decarboxylase (GAD) and a tyrosine phosphatase-like molecule (IA-2). We have studied both HLA class I and class 2 allele distributions in diabetic probands and autoantibody positive individuals in members of 452 families recruited for the Australian type I diabetes DNA repository. The results demonstrate that progression to autoimmunity as measured by the appearance of autoantibodies is strongly associated with the class 2 alleles DRB1*03 and DRB*04 and with DRB1*03/04 heterozygosity. In contrast, the progression to clinical disease appears associated with class I alleles A24, A30 and B18 while A1, A28, B14 and B56 appear negatively associated. The class 2 alleles appear to have a minimal role in the progression from autoantibody positivity to clinical disease. These results are consistent with the view that CD4(+) T cells responding to peptides in the context of class 2 molecules are responsible for initiating autoantibody production, while the destruction of islet cells leading to clinical expression of the disease is the function of CD8(+) T cells recognizing relevant peptides in the context of class I molecules.
- Publisher
- BLACKWELL MUNKSGAARD
- Keywords
- INHIBITORY RECEPTORS; T-LYMPHOCYTES; INSULIN; MELLITUS; IDDM; EXPRESSION; RISK; PREDICTION; RELATIVES; SUSCEPTIBILITY
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- Refer to copyright notice on published article.
Creation Date: 2003-02-01 12:00:00