山东地区汉族人群KIR基因多态性分析

目的 分析山东地区汉族人群杀伤细胞免疫球蛋白样受体(KIR)基因多态性及基因型和单倍型多态性,为进一步研究KIRs与疾病的关系奠定基础.方法 采用序列特异性引物PCR法(PCR-SSP)对412例山东地区无血缘关系的汉族健康志愿者进行KIR基因频率检测及基因型和单倍型分析.结果 ①KIR基因频率:可检测到目前已知的18种KIR基因;所有个体均检测到3个框架基因(2D14、3DL2、3D13)以及KIRZ,其基因频率均为100%.3DP1、2DL3、2DL1、3DL1和2DS4基因较为常见,频率分别为99.03%、98.79%、98.79%、98.79%、96.84%;而2DL2、2DS2、3DP1v基因频率较低.②KIR基因型频率:共检出基因型28种,以AJ(2,2)、AF(1,2)型最常见,其次为AH(5,2)、G(4,5)、M(1,5);另外有11种基因型在自人中尚未见报道.③KIR基因单倍型频率:共检出单倍型16种,最常见的是单倍型2,频率为46.36%;其次为单倍型1,频率为25.61%.结论 山东地区汉族人群有其独特的KIRs基因频率、基因型频率和单倍型频率分布;本研究可为进一步研究KIRs与疾病的相关性提供依据.     

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。     

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。     

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-HLA基因多态性与散发性急性戊型肝炎的关系

目的探讨杀伤性免疫球蛋白样受体(KIR)及其配体人类白细胞抗原(HLA)的基因多态性与散发性急性戊型肝炎(AHE)的相关性。方法收集2015年8月-2016年9月期间于复旦大学附属公共卫生临床中心肝炎一科住院的AHE患者42例,另招募健康受试者30例作为对照组。提取入组对象外周血基因组DNA,采用序列特异性引物PCR法扩增KIR基因,并利用Sanger测序法对HLA进行基因分型,分析KIR-HLA分布与散发性AHE的关系。计数资料组间比较采用χ~2检验。结果两组均可检测到16种KIR基因(包括抑制型受体基因2DL1-3、2DL5、3DL1-3,激活型受体基因2DS1-5、3DS1,较特殊的抑制型/激活型受体基因2DL4,内参基因DRB1及假基因2DP1),同时HLA-B(包括HLA-Bw4、HLA-Bw6、HLA-Bw4/Bw6)、HLA-C(包括HLA-C1/C1、HLA-C1/C2、HLA-C2/C2)亦可检测。AHE患者中抑制型基因KIR 2DL3/2DL5/3DL2/3DL3出现的频率显著低于对照组(64.3%vs 93.3%,P0.05;23.8%vs 56.7%,P0.05;71.4%vs 100%,P0.05;69.0%vs 100%,P0.05);AHE患者HLA-C1/C2和3DL1/HLA-Bw4基因的出现频率低于对照组(19.0%vs 40.0%,P0.05;45.2%vs 73.3%,P0.05);另外,AHE患者中HLA-C1/C1基因出现的频率高于对照组(71.4%vs 46.7%,P0.05)。结论抑制型基因KIR 2DL3/2DL5/3DL2/3DL3,HLA-C1/C1、C1/C2和3DL1/HLA-Bw4的基因分布差异可能与HEV感染导致散发性AHE有一定关系。     

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.     

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。     

KIR2DL1和KIR2DL3在炎症性肠病患者外周血和肠组织中的表达

背景：KIR2DL1和KIR2DL3属抑制性杀伤细胞免疫球蛋白样受体家族成员,在一些免疫相关疾病中发挥重要作用.目前,KIR2DL1和KIR2DL3在炎症性肠病（IBD）中的研究还相对较少.目的：探讨KIR2DL1和KIR2DL3在IBD患者外周血和肠组织中的表达及其临床意义.方法：收集111例溃疡性结肠炎（UC）患者、101例克罗恩病（CD）患者和110例健康志愿者.以聚合酶链反应-序列特异性引物（PCR-SSP）法检测外周血中KIR2DL1和KIR2DL3表达,并分析其与患者临床特征的关系.以免疫组化染色检测肠组织中KIR2D L1蛋白表达.结果：UC组外周血KIR2DL1和KIR2DL3表型频率均显著低于正常对照组（P＜0.05）;CD组KIR2DL1表型频率显著低于正常对照组（P=0.026）,但两组KIR2DL3表型频率无明显差异（P＞0.05）.KIR2D L1和KIR2DL3表型频率与UC和CD患者的疾病活动性、病情严重程度和病变部位均无关.UC和CD患者肠组织中KIR2DL1蛋白表达均明显低于对照组（P＜0.001）.结论：IBD患者中存在KIR2DL1基因和蛋白的低表达,提示其在IBD的免疫发病机制中可能起重要作用.     

SCNN1A基因多态性与土家族、苗族及汉族人群原发性高血压相关性的研究

目的:探讨上皮细胞钠通道α亚基(SCNN1A)基因单核苷酸多态性位点rs2228576与湘西土家族、苗族和汉族人群原发性高血压(EH)的相关性。方法:用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析土家族(120例)、苗族(117例)和汉族(125例)人群EH患者(EH组)与正常人群[正常对照组(土家族119例、苗族125例、汉族122例)]SCNN1A等位基因频率分布状况。结果:土家族、苗族和汉族均存在3种AA、AG及GG基因型;土家族、苗族和汉族正常对照组基因型频率分别为(0.109,0.538,0.353;0.152,0.472,0.376;0.164,0.541,0.295);各族EH组与正常对照组基因型频率差异均无统计学意义(χ2=5.662,P>0.843);等位基因频率差异均无统计学意义(χ2=3.538,P>0.618)。结论:3个民族均存在SCNN1A基因rs2228576多态性位点,但该多态性位点与3个民族EH无明显相关性。     

Fcγ受体ⅢB基因多态性与系统性红斑狼疮易感性及临床表型的相关性研究

目的研究Fcγ受体ⅢB基因多态性在黄河三角洲汉族人群中的分布,探讨其多个位点的基因多态性与SLE易感性及临床表型的相关性。方法选择2017年1月至12月于山东省滨州医学院附属医院就诊的144例SLE患者作为试验组,同期健康志愿者150名作为对照组,收集全血标本和临床资料、试验室检查资料,采用单碱基延伸法PCR技术提取基因组脱氧核糖核酸(DNA),采用质谱法进行单核苷酸多态性(SNP)分型检测,应用SPSS 25.0软件进行χ^2检验,分析Fcγ受体ⅢB基因各位点基因多态性与SLE易感性及临床表型的关系。结果①在试验组和对照组中,rs115878669 CT、TT基因型频率分别为50.7%、64.0%,23.6%、10.0%,差异有统计学意义(χ^2=5.3,P=0.021;χ^2=9.8,P=0.002);rs147574249 TT基因型频率分别为17.4%、8.0%,差异有统计学意义(χ^2=5.9,P=0.016);rs199705513 GG、GA基因型频率分别为20.8%、10.0%,59.0%、70.0%,差异有统计学意义(χ^2=6.7,P=0.010;χ^2=3.9,P=0.049);rs77717968 CA基因型频率分别为30.6%、46.0%,差异有统计学意义(χ^2=7.4,P=0.007)。②在试验组中,rs115878669位点杂合子CT基因型频率在血液系统受累和不受累组分别为37.2%、56.4%,差异有统计学意义(χ^2=4.5,P=0.035);在血小板减少组与血小板正常组中,rs114531649位点AG基因型频率分别为79.2%、50.0%,差异有统计学意义(χ^2=6.8,P=0.009),GG基因型频率分别为4.2%、25.8%,差异有统计学意义(χ^2=4.3,P=0.039),rs147574249位点CC基因型频率分别为4.2%、25.8%,差异有统计学意义(χ^2=5.4,P=0.020),CT基因型频率分别为79.2%、56.7%,差异有统计学意义(χ^2=4.2,P=0.040),rs115878669位点CT基因型频率分别为70.8%、46.7%,差异有统计学意义(χ^2=4.7,P=0.031),rs199705513位点AA基因型频率分别为4.2%、23.3%,差异有统计学意义(χ^2=4.6,P=0.033),rs77717968位点AA基因型频率分别为4.2%、26.7%,差异有统计学意义(χ^2=4.5,P=0.033),TT基因型频率分别为25.0%、9.2%,差异有统计学意义(χ^2=4.8,P=0.028),其他比较无统计学意义(P>0.05)。在关节受累组与关节未受累组中,rs114531649位点纯合子GG基因型频率分别为31.2%、15.7%,差异有统计学意义(χ^2=4.9,P=0.027),rs147574249位点纯合子CC基因型频率分别为31.2%、15.7%,差异有统计学意义(χ^2=4.9,P=0.027),rs199705513位点纯合子AA基因型频率分别为29.5%、13.2%,差异有统计学意义(χ^2=5.8,P=0.016),rs61803007位点纯合子CC基因型频率分别为32.8%、16.9%,差异有统计学意义(χ^2=4.9,P=0.026),杂合子TC基因型频率分别为67.2%、83.1%,差异有统计学意义(χ^2=4.9,P=0.026),rs77717968位点纯合子AA基因型频率分别为31.2%、16.9%,差异有统计学意义(χ^2=4.1,P=0.044),其他比较差异无统计学意义(P>0.05)。rs146653557位点杂合子TC基因型基因型频率在有浆膜炎组和无浆膜炎组分别为39.4%、75.0%,差异有统计学意义(χ^2=4.3,P=0.037),其他比较差异无统计学意义(P>0.05)。在RF升高组与RF未升高组中,rs428194位点CG基因型频率分别为53.8%、22.9%,差异有统计学意义(χ^2=12.7,P=0.0004),GG基因型频率分别为46.2%、77.1%,差异有统计学意义(χ^2=12.7,P=0.0004),rs61803004位点GG基因型频率分别为46.2%、78.1%,差异有统计学意义(χ^2=13.7,P=0.0002),GT基因型频率分别为46.2%、21.0%,差异有统计学意义(χ^2=9.0,P=0.0027),TT基因型频率分别为7.7%、1.0%,差异有统计学意义(χ^2=4.8,P=0.029),rs61803008位点CT基因型频率分别为46.2%、23.8%,差异有统计学意义(χ^2=6.8,P=0.0092),TT基因型频率分别为46.2%、74.3%,差异有统计学意义(χ^2=10.1,P=0.0015)。结论Fcγ受体ⅢB基因相关位点可能与SLE的疾病易感性及临床表型有关。     

The KIR2DS2/DL2 genotype is associated with adult persistent/chronic and relapsed immune thrombocytopenia independently of FCGR3a-158 polymorphisms

Adult immune thrombocytopenia (ITP) is a heterogeneous disease and its immunobiology is incompletely understood. Establishing associations between candidate genes and ITP susceptibility may provide insight into pathogenesis. Previous studies have associated overrepresentation of FCGR3a-V158 allele with pediatric ITP. We prospectively accrued DNA from 102 adult patients with persistent/chronic or relapsed primary ITP identified by defined criteria. The distribution of KIR2 genes and polymorphisms of FCGR3a, both associated with autoimmunity, were compared with 105 healthy white individuals. Results were stratified by ethnicity. Carriers of the KIR2DS2/KIR2DL2 genotype [KIR2DS2/KIR2DL2 versus KIR2DS2/KIR2DL2 and KIR2DS2/KIR2DL2; odds ratio (OR) 2.51, P = 0.002] were overrepresented. In addition, frequency of the high-binding affinity FCGR3a-V/V158 genotype (VV versus VF/FF; OR = 3.05, P = 0.007) was increased, whereas that of the FCGR3a-F158 allele was reduced (OR = 2.58, P = 0.00.002). In a regression model to adjust for age, sex and the effects of the other gene, the KIR2 genotype independently conferred increased susceptibility from the FCGR3a-158 polymorphisms. In a comparison of healthy controls and a tightly defined cohort of adult ITP patients, the KIR2DS2/KIR2DL2 genotype was found to be associated with ITP independently of FCGR3a-158 polymorphisms. Further studies are required to establish the mechanistic basis for these observations and their potential impact on immune-based therapies.     

Association between KIR Genes and Efficacy of Treatment of HBeAg-Positive Chronic Hepatitis B Patients with Entecavir

Background: Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China. However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not respond to ETV therapy. Objective: To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion in HBeAg positive CHB responder patients treated with ETV. Methods: Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was performed to genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients which 59 were defined as the complete response group (CRG) to the treatment with ETV and 139 were defined as null or partial response group (NPRG). Results: The frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030, OR=1.57,95%CI=2.36-1.05 and P=0.018, OR=1.773,95%CI=2.77-1.13, respectively), while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower (P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and P=0.035, OR=0.641, 95%CI =0.96-0.43, respectively) in HBeAg-positive CHB patients than those in healthy controls. The frequency of KIR2DS3 gene was significantly higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949, 95%CI=3.65-1.04, respectively). Conclusion: Patients with KIR2DS3 might have negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and KIR3DS1 might have advantage in the therapy with ETV.     

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.     

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.     

Association of KIR genotype with susceptibility to HLA-B27-positive ankylosing spondylitis

Objective

Recent studies have explored the role of killer cell immunoglobulin-like receptors (KIRs) in chronic autoimmune diseases. The purpose of this study was to demonstrate whether KIR genes contribute to the pathogenesis of ankylosing spondylitis (AS) in Chinese populations.

Methods

Sixteen KIR genes were genotyped from 60 unrelated patients with AS and 60 HLA-B27-positive matched healthy controls by PCR-SSP. The frequencies of the KIR alleles and genotypes in the AS and control groups were assessed by the χ ² test.

Results

Our results showed that the frequency of the activator receptor KIR3DS1 gene in the AS group was significantly increased compared to the controls (χ ² = 5.263, P = 0.006, OR = 3.059, 95 % CI = 1.357–6.896). Moreover, the frequency of the KIR3DL1/3DS1 genotype was greater in the AS group than in the control group (P = 0.039, OR = 3.059, 95 % CI = 1.357–6.896). In contrast, the frequency of the no KIR3DL1/no 3DS1 genotype was lower in patients with AS compared with the controls (P = 0.032, OR = 0.110, 95 % CI = 0.013–0.911).

Conclusion

KIR3DS1, in addition to HLA-B27, may play an important independent role in the pathogenesis of AS in the Chinese population.     

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.

     

Inhibitory Killer Cell Immunoglobulin-Like Receptor KIR3DL1 in Combination with HLA-B Bw4iso Protect against Ankylosing Spondylitis

Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis (AS) susceptibility, alone or in combination. Methods: We typed 40 AS patients and 40 normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-B Bw4thero, HLA-B Bw4iso and HLA-A Bw4 alleles by PCR-SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis. Results: The frequency of HLA-B Bw4iso but not HLA-B Bw4thero and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-Biso gene was reduced in patients with AS compared to healthy controls (p<0.009). Conclusion: We conclude that HLA-B Bw4iso, the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease