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Contribution of functional KIR3DL1 to ankylosing spondylitis

Cellular & Molecular Immunology 2010年第6期7卷 471-476页

作者： Ivan V Zvyagin Ilgar Z Mamedov Olga V Britanova Dmitriy B Staroverov Evgeni L Nasonov Anna G Bochkova Anna V Chkalina Alexei A Kotlobay Dmitriy O Korostin Denis V Rebrikov sergey lukyanov Yuri B Lebedev Dmitriy M Chudakov Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry RASMoscowRussia Institute of Rheumatology RAMSMoscowRussia DNA-Technology JSC MoscowRussia Vavilov Institute of General Genetics MoscowRussia

Increasing evidence points to a role for killer immunoglobulin-like receptors(KIRs)in the development of autoimmune *** particular,a positive association of KIR3DS1(activating receptor)and a negative association of KIR3DL1(inhibitory receptor)alleles with ankylosing spondylitis(AS)have been reported by several ***,none of the studies analyzed these associations in the context of functionality of polymorphic *** better understand how the KIR3DL1/3DS1 genes determine susceptibility to AS,we analyzed the frequencies of alleles and genotypes encoding functional(KIR3DL1*F)and non-functional(KIR3DL1*004)*** genotyped 83 AS patients and 107 human leukocyte antigen(HLA)-B27-positive healthy controls from the Russian Caucasian population using a two-stage sequence-specific primer PCR,which distinguishes KIR3DS1,KIR3DL1*F and KIR3DL1*004 *** the patients carrying two functional KIR3DL1 alleles,those alleles were additionally genotyped to identify KIR3DL1*005 and KIR3DL1*007 alleles,which are functional but are expressed at low ***3DL1 was negatively associated with AS at the expense of KIR3DL1*F but not of KIR3DL1**** finding indicates that the inhibitory KIR3DL1 receptor protects against the development of AS and is not simply a passive counterpart of the segregating KIR3DS1 allele encoding the activating ***,analysis of genotype frequencies indicates that the presence of KIR3DS1 is a more important factor for AS susceptibility than the absence of KIR3DL1**** activation of either natural killer(NK)or T cells via the KIR3DS1 receptor can be one of the critical events in AS development,while the presence of the functional KIR3DL1 receptor has a protective ***,even individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed at high levels could develop AS.

关键词： ankylosing spondylitis autoimmune disease HLA-B27 KIR KIR3DL1 KIR3DS1 KIR3DL1*004 NK cell T cell

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