NDLI: Autoantibody epitopes to the smaller isoform of glutamate decarboxylase do not differ in Swedish and Japanese type 1 diabetes patients and may be associated with high-risk human leucocyte antigen class II alleles

Content Provider	PubMed Central
Author	Maruyama, T. Oak, S. Hall, T. R. Banga, J. P. Ortqvist, E. Ettinger, R. A. Endl, J. Hampe, C. S.
Copyright Year	2007
Abstract	Type 1 diabetes (T1D) is an autoimmune disease with a strong human leucocyte antigen (HLA) class II association. Depending on geographic locations, the disease-associated HLA class II alleles vary. We evaluated the β cell-specific autoimmunity reflected in autoantibodies directed to the smaller isoform of glutamate decarboxylase (GAD65) in Japanese and Swedish T1D patients. GAD65Ab epitope specificities were assessed using GAD65-specific recombinant Fab. GAD65Ab epitope specificities did not differ between Swedish and Japanese patients. Only recognition of the MICA-4-defined middle epitope was significantly stronger in the Japanese T1D patient group compared to the Swedish T1D patients (P = 0·001). Binding to the b96·11-defined middle epitope was substantial in both groups and showed significant associations with high-risk HLA class II haplotypes. In the Japanese T1D group the association was with haplotype DRB10802-DQB10302 (P = 0·0008), while in the Swedish T1D patients binding to the b96·11-defined epitope as associated with the presence of high-risk HLA genotypes DR3-DQB10201 and/or DR4-DQB10302 (P = 0·02). A significant association between reduction in binding in the presence of recombinant Fab (rFab) DPD and high-risk allele DQB1*0201 was found (P = 0·008) in the Swedish T1D patients only. We hypothesize that epitope-specific autoantibodies effect the peptide presentation on HLA class II molecules by modulating antigen uptake and processing. Molecular modelling of the high-risk HLA class II molecules will be necessary to test whether these different molecules present similar peptide-binding specificities.
Related Links	http://dx.doi.org/10.1111/j.1365-2249.2007.03527.x
Ending Page	421
Page Count	6
Starting Page	416
File Format	PDF
ISSN	00099104
e-ISSN	13652249
Journal	Clinical and Experimental Immunology
Issue Number	3
Volume Number	150
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2007-10-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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