KIR基因多态性与病毒感染性疾病相关研究进展

杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor, KIR)主要表达于 NK 细胞和部分 T 细胞表面,属于免疫球蛋白样超家族的一系列分子,能够与靶细胞表面的人类白细胞抗原 I 类分子相互作用,具有高度多态性,对于调控 NK 细胞和 T 细胞参与免疫应答反应具有重要意义,本文现将 KIR 基因多态性与几种发病率较高的病毒感染性疾病的研究进展进行综述。     

杀伤细胞免疫球蛋白样受体基因多态性与白塞病的关联性分析

目的探讨杀伤细胞免疫球蛋白样受体(KIR)基因多态性与白塞病(BD)发生是否存在关联。方法采用聚合酶链反应(PCR)／序列特异性引物(SSP)方法调查上海地区汉族95例白塞病患者和87名正常对照KIR基因位点的多态性。结果白塞病例组中KIR3DL1基因的频率(0．728)比对照组 (1．00)显著降低(RR=0．067,P=0．009);而其他各KIR基因频率与对照组相比差异无统计学意义。KIR单倍型频率、基因型频率与对照组相比差异也无统计学意义。结论上海地区汉族白塞病的发生可能与 KIR3DL1基因之间呈负相关。     

杀伤细胞免疫球蛋白样受体基因多态性与血清阴性脊柱关节病的关联性研究

目的 探讨杀伤细胞免疫球蛋白样受体(KIR)基因多态性与血清阴性脊柱关节病(SpA)的发生是否存在关联。方法 采用聚合酶链反应(PCR)／系列特异性引物(SSP)方法，调查上海地区197例HLA—B27( )SpA患者和87名种族匹配的正常对照KIR基因位点的多态性。结果 SpA病例组中KIR3DLl基因的频率(0．763)比对照组(1．00)显著降低(RR=0．76，P=0．003)，两个假基因KIR2DRI和KIR3DPI的频率较对照组明显升高(RR=1．1，P=0．004)，而其他各KIR基因频率差异无显著性。结论 KIR3DL1基因与SpA的发生可能存在负相关。     

汉族健康人群KIR分布对异基因造血干细胞移植供者选择的影响

目的探讨杀伤细胞免疫球蛋白样受体（KIR）在中国人群中的分布规律及其对异基因造血干细胞移植供者选择的影响。方法采用序列特异性引物PCR（PCR-SSP）分型技术检测了79例汉族人群中KIR的基因型分布、74例异基因造血干细胞移植供受者对KIR及HLA基因型。结果KIR2DL1的基因分布频率为100％,KIR2DL2为20％,KIR2DL3为100％,KIR3DLI为94．81％。95．9％的供者携带与异基因造血干细胞移植关系密切的三组KIR受体。结论汉族人群具有独特的KIR分布规律,KIR2DL1、KIR3DL1是在中国人群异基因造血干细胞移植中起主要作用的KIR受体。     

KIR多态性与相关疾病的研究进展

杀伤细胞免疫球蛋白样受体（KIR）主要表达于NK细胞和部分T细胞表面，属于免疫球蛋白样超家族的一系列分子，具有高度多态性。KIR编码基因定位于人类染色体19q13．4的白细胞受体复合物中，包括胞外区、跨膜区及胞内区，胞外区含有2个或3个免疫球蛋白样结构域，分别称为KIR2D和KIR3D。     

系统性红斑狼疮患者杀伤细胞免疫球蛋白样受体基因型分析

目的探讨杀伤细胞免疫球蛋白样受体（KIR）基因型在系统性红斑狼疮（SEE）患者中的分布规律。方法采用序列特异性引物聚合酶链反应（PCR—SSP）法，分析93例SEE患者和123例无血缘关系的健康对照组KIR基因型。结果SEE组中3DL3＋，2DS2^-，2DL2^＋，2DL3^＋，KIRZ^＋，2DL1^＋，2DL4＋．3DL1^＋,3DS1^-，2DL5^-，2DS3^-，2DS5^-，2DS1^＋，2DS4^＋，3DL24^＋因型阳性率最高，占16．13％（与对照组比较P〈0．01），对照组中3DL3^＋，2DS2^-，2DL2^-，2DL3^＋，KIRZ^＋，2DL1^＋，2DL4^＋，3DL1^＋，3DS1^-，2DL5^-，2DS3^-，2DS5^-．2DS1^-，2DS4^＋，3DL2^＋因型阳性率最高，占19．51％（P=0．004），差异均有统计学意义。结论SLE与正常对照组中KIR基因型分布差异可能参与SLE发病。     

ADRB2基因多态性/单倍型与中国南方汉族人群支气管哮喘相关表型的关系

目的 研究中国南方汉族人群β2肾上腺素能受体(ADRB2)基因单核苷酸多态性/单倍型与支气管哮喘(简称哮喘)相关表型的相关性.方法 采用Taqman探针法对379例哮喘患者和435例健康对照者ADRB2基因6个位点(T-2387C、5'LC Arg19 Cys、Arg16Gly、Glu27Gln、Thr164Ile和C523A)进行基因分型,并确定其单倍型.采用酶联免疫吸附(enzyme linked immunosorbent assay,ELISA)法检测血清总IgE.结果 164位均为野生型纯合基因型,未检测到突变型等位基因,未纳入统计分析.T-2387C、5'LC Arg19 Cys、Arg16Gly、Glu27Gln和C523A基因型频率和单倍型频率在轻+中度哮喘组与重度哮喘组间分布差异均无统计学意义(x2分别为:2.45,4.12,0.43,5.81,0.44;2.39,0.80,1.42,0.20,P值均＞0.05),在夜间哮喘组与非夜间哮喘组间分布差异亦无统计学意义(x2分别为:0.77,1.51,1.68,1.51,1.03;1.05,0.45,1.01,0.40,P值均＞0.05).哮喘组血清总IgE[(83.95±67.35) μg/L]高于正常健康组[(66.12±61.27)μg/L)],各位点基因型间血清总IgE水平比较差异无统计学意义(x2或Z值分别为:1.88,-1.21,1.677,-1.17,1.93,P值均＞0.05),5个位点组成的4种纯合型单倍型间血清总IgE水平比较差异亦无统计学意义(x2为1.33,P＞0.05).同种基因型的哮喘患者血清总IgE水平与哮喘病情严重程度及夜间哮喘差异均无统计学意义(Z值分别为:-0.73,-0.06,-0.64,-1.35,-1.82,-1.15,-0.05,-1.15,-1.37,-1.78,-0.44,-0.01,-0.35;-1.48,-0.93,-0.45,-0.42,-0.48,-0.11,-0.09,-0.80,-0.27,-0.26,-0.30,-0.23,-1.03,P值均＞0.05).但将不同严重程度哮喘组分层分析发现,重度哮喘组Arg/Cys19+Cys/Cys19、Gln/Glu27+Glu/Glu27有更高的血清IgE水平.结论 ADRB2基因单核苷酸多态性/单倍型与哮喘严重程度、夜间哮喘无显著相关性,但-47、79位可能与重度哮喘患者血清总IgE有关.     

恩替卡韦治疗慢性HBV感染者KIR基因多态性与疗效的相关性研究

目的探讨慢性HBV感染者杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor,KIR)基因多态性及其与应用恩替卡韦疗效差异相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)法,对60例应用恩替卡韦治疗的慢性HBV感染者(试验组)和60例健康对照者(对照组)的KIR基因进行基因分析,比较试验组和对照组的差异。60例患者中18例为治疗完全应答者(完全应答组),42例为非完全应答者(非完全应答组),比较2组之间差异。结果通过试验组和对照组的16种KIR基因分析,框架基因KIR2DL4、3DL2、3DL3和3DP1存在于所有个体中,其基因频率均为1.0。试验组KIR 2DS2和KIR2DS3基因型频率高于对照组(P值依次为0.038和0.035);完全应答组KIR2DS1、KIR3DS1和KIR2DL5基因型频率高于非完全应答组(P值依次为0.010、0.029和0.018)。结论 KIR2DS2、KIR2DS3可能是HBV的易感基因型,KIR2DS1、KIR3DS1、KIR2DL5可能与恩替卡韦抗HBV治疗有效应答有关。     

中国北方汉族人群哮喘患者受体基因多态性研究

支气管哮喘是一种多基因遗传病 ,本研究通过检测支气管哮喘患者 β2 肾上腺素受体基因第 46、79位点及高亲和力免疫球蛋白Ｅβ 链受体基因第 5 189、5 191、5 195、6 843位点的多态性 ,探讨其与支气管哮喘发病的相关性。一、对象与方法1.对象 :哮喘组 :支气管哮喘患者 5 5例 ,男 30例 ,女 2 5例 ,年龄 2 0～ 6 6岁。诊断符合中华医学会呼吸病学分会1997年制定的诊断标准。根据临床症状和所需药物情况 ,将患者分为轻度 (包括间歇发作 )和中重度 ,轻度患者 2 5例 ,中重度患者 30例。正常对照组 :正常健康成人 38例 ,男 15例 ,女 2 3例 ,年龄 2…     

杀伤细胞免疫球蛋白样受体基因多态性与Graves病相关

采用PCR-SSP的方法对96例Graves病患者和96例相匹配的正常人的11个杀伤细胞免疫球蛋白样受体（KIR）基因位点进行检测。结果显示Graves病例组中KIR2DS4基因的频率较对照组明显降低（0．500vs0．856，P〈0．01，RR=0．58），提示KIR2DS4基因可能与Graves病的发病相关。     

HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis

RATIONALE: In idiopathic bronchiectasis, lung inflammation and chronic bacterial infection lead to progressive lung damage. A possible role for natural killer (NK) cells is suggested by the observation that familial bronchiectasis occurs in a rare group of individuals with impaired HLA class I expression and consequent NK cell dysfunction. OBJECTIVE: Because the HLA-C locus and killer cell immunoglobulin-like receptors (KIRs) are of key importance for NK cell recognition, we analyzed HLA-C/KIR combinations by genotyping patients with idiopathic bronchiectasis. METHODS: Genomic DNA from 96 individuals with idiopathic bronchiectasis and 101 control subjects was analyzed by polymerase chain reaction with sequence-specific primers. High-resolution HLA-C genotyping was performed in addition to KIR analysis. RESULTS: HLA-Cw*03 alleles and, in particular, HLA-C group 1 homozygosity are associated with the presence of bronchiectasis. Analysis of the relationship between HLA-C and KIR genes suggests a shift to activatory NK cell function. CONCLUSION: This is the first demonstration of genetic susceptibility in idiopathic bronchiectasis. The association with HLA-C group 1 homozygosity, and the interplay between HLA-C and KIR genes, argue for a role for NK cells in the progressive lung damage seen in this disease. This will require further investigation using functional studies.     

Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis

OBJECTIVE: Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA. METHODS: The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody-positive Japanese subjects (43 patients with MPA and 239 healthy controls). RESULTS: The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06-0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA-Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18-4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA-B and KIR2DL1/ HLA-C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory. CONCLUSION: The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections.     

炎症性肠病患者抑制性杀伤细胞免疫球蛋白样受体基因多态性分析

目的 分析炎症性肠病(inflammatory bowel disease,IBD)患者抑制性杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-like receptor,iKIR)基因多态性,探讨iKIR基因多态性与IBD的关联性.方法 收集100例溃疡性结肠炎(UC)、52例克罗恩病(CD)患者和106名种族匹配的健康对照者外周血DNA标本,采用序列特异性引物聚合酶链反应(PCR-SSP)方法,分析上述对象iKIR基因位点的多态性,计算iKIR基因表型频率和基因频率,比较IBD患者与健康对照者间的差异.结果 iKIR基因(包括KIR2DL1、KIR2DL2、KIR2DL3、KIR2DL4、KIR2DL5、KIR3DL1、KIR3DL2、KIR3DL3)在IBD患者和健康对照组均有不同程度的表达.UC患者KIR2DL1和KIR2DL3表现型频率比健康对照组显著降低(P=0.001),而KIR2DL2、KIR2DL4、KIR2DL5、KIR3DL1、KIR3DL2和KIR3DL3表现型频率与健康对照组比较差异无统计学意义(P＞0.05).CD患者KIR2DL1表现型频率比健康对照组显著降低(P=0.007),而其余iKIR基因表现型频率与健康对照组比较差异无统计学意义(P＞0.05).结论 KIR2DL1和KIR2DL3表现型频率在UC患者中显著下降,提示其与UC的易感性有密切关系; 而KIR2DL1基因可能与CD易感性密切相关.     

Association of killer cell immunoglobulin-like receptors with scleroderma

OBJECTIVE: Scleroderma is an autoimmune disorder of unknown etiology. A genetic contribution has been demonstrated, and genes influencing activation of the immune system have been potentially identified as candidate genes in this process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that are involved in the activation of T cells and natural killer cells is highly variable. Recently, an association of KIR2DS2 with vasculitis in patients with rheumatoid arthritis has been reported. Because scleroderma is characterized by an involvement of the vascular system, we sought to determine whether KIR2DS2 is associated with scleroderma. METHODS: We typed 9 KIR genes in 102 patients with scleroderma and in 100 blood donors, using polymerase chain reaction on genomic DNA. RESULTS: Twelve patients with scleroderma, compared with only 2 blood donors, had KIR phenotypes characterized by the presence of the activating KIR2DS2 and the absence of the corresponding inactivating KIR2DL2 (P = 0.005). CONCLUSION: The genetic combination of KIR2DS2+ and KIR2DL2- is associated with scleroderma.     

The investigation of killer cell immunoglobulin-like receptor genotyping in patients with systemic lupus erytematosus and systemic sclerosis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls (p values <0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p?=?0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined (p values?<?0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients (p values <0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE.