HLA genes associated with autoimmunity and progression to disease in type 1 diabetes

B.D. Tait, P.G. Colman, Grant Morahan, L. Marchinovska, E. Dore, S. Gellert, M.C. Honeyman, K. Stephen, A. Loth

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57 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)146-153
JournalTissue Antigens
Issue number2
Publication statusPublished - 2003


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