Can MHC class II genes mediate resistance to type 1 diabetes?

Immunology and Cell Biology
P PriceR J Allcock

Abstract

Numerous studies have associated carriage of HLA-DRB1*1501, DQA1*0102 and DQB1*0602 (DR15, DQ6) with dominant resistance to type 1 diabetes and have concluded that one or more of the component HLA class II molecules mediate this effect. Mechanisms for MHC class II-mediated resistance to diabetes have been proposed from studies of transgenic mice, usually using the diabetes-prone non-obese diabetic (NOD) strain. However, these studies have not reached any consensus on a plausible mechanism. In this study we question why the role of central MHC genes in resistance to diabetes has not been addressed, as the central MHC carries markers of susceptibility to diabetes in linkage disequilibrium with several genes with known or putative immunoregulatory functions. To illustrate the type of studies required to address this issue, we selected diabetes patients and control subjects for carriage of HLA-DR15 and the C allele at position +738 in the inhibitor of kappa B-like gene (IKBL). These alleles mark the 7.1 haplotype (HLA-A3, B7, IKBL738*C, DR15, DQ6). HLA-DR15 was the most effective marker of resistance, but an effect may be evident with IKBL738*C in a larger study. Moreover, carriage of the entire haplotype was particularly rare in p...Continue Reading

References

Jan 1, 1992·Immunogenetics·C M Milner, R D Campbell
Aug 1, 1992·Human Immunology·M A Degli-EspostiR L Dawkins
Oct 1, 1994·Diabetes Research and Clinical Practice·T Awata, Y Kanazawa
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R M SlatteryB Charlton
Jan 1, 1994·Tissue Antigens·A Svejgaard, L P Ryder
May 3, 1996·Cell·R Tisch, H McDevitt
Jan 23, 1999·Current Opinion in Immunology·H O McDevitt
May 20, 1999·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·J GrahamG Dahlquist
Dec 20, 1999·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·G PrevostC Besmond
Mar 16, 2000·Human Immunology·C B Sanjeevi
Aug 12, 2000·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·V B MatthewsP Price
Jan 13, 2001·Current Opinion in Immunology·S Gallucci, P Matzinger
Apr 4, 2001·The Journal of Clinical Investigation·L WenF S Wong

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Citations

Jan 3, 2012·Rheumatology·Hector ChinoyUNKNOWN UK Adult Onset Myositis Immunogenetic Consortium and UK Juvenile Dermatomyositis Research Group
Aug 25, 2012·World Journal of Diabetes·Youssef M MosaadFarha A El-Chennawi
Sep 23, 2010·Human Immunology·Hakbany MananAwadalla Sitelbanat
Aug 12, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Aldo J Montano-LozaAndrew L Mason

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