隐匿性HBV感染无偿献血人群KIR基因多态性的特征分析

目的探讨无偿献血人群中隐匿性乙型肝炎病毒感染(OBI)献血者的KIR基因多态性及其特征分析。方法筛选2016年6月-2019年6月重庆市血液中心无偿献血人群中OBI献血者105例,采集外周血样提取DNA并作KIR基因分型;通过与国际等位基因网站公布的KIR基因型数据库对照分析,判断KIR基因型ID及单体型,计算基因表型频率(某种基因出现例数/总例数)、基因型频率(某中基因型出现例数/总例数)和基因频率(F)=√1-基因表型频率)。计数资料组间比较采用χ^2检验。结果105例OBI献血者均含有的KIR基因有2DL4、3DL2、3DL3和假基因3DP1;F>70%的KIR基因有2DL1、2DL3、3DL1、2DS4和假基因2DP1,其中KIR 2DS4第5外显子存在缺失的F为26.32%。F<30%的基因有2DL2、2DL5、2DS1、2DS2、2DS3、2DS5、3DS1。OBI献血人群分别与重庆汉族、河北汉族、江苏汉族和拉萨藏族比较,KIR 2DL3基因频率均降低(χ^2分别为9.598、12.236、13.719、10.974,P值均<0.05);OBI献血人群2DL2、2DL5、2DS2、2DS3与乌市维族比较差异均有统计学意义(χ2值分别为16.215、6.981、19.498、11.819,P值均<0.05);OBI献血人群2DL2、2DS1、2DS2、2DS3、2DS4与高加索人比较差异均有统计学意义(χ^2分别为22.477、3.877、34.937、6.909、4.271,P值均<0.05);OBI献血人群与重庆汉族相比,KIR 2DS4*del频率升高(χ^2=12.911,P<0.05)。OBI献血人群与长期慢性HBV感染组相比,2DS2、2DS3频率降低(χ^2分别为13.005、8.289,P值均<0.05),但2DS4、3DL1频率升高(χ^2分别10.032、3.865,P值均<0.05);OBI献血人群与强直性脊柱炎组相比,2DL3、2DS3基因频率降低(χ^2分别为7.851、16.504,P值均<0.05);OBI献血人群与男男同性恋HIV-AIDS组相比,2DS4、3DL1基因频率升高(χ^2分别为15.491、4.475,P<0.05);OBI献血人群与散发性急性戊型肝炎组相比,2DL1、2DL2、2DL3、2DL4、2DL5、2DS4、3DL2、3DL3、2DP1差异均有统计学意义(χ2分别为4.448、30.934、17.942、15.638、4.227、13.802、32.667、35.653、36.566,P值均<0.05)。共发现21种KIR基因型,其中基因型AA1(49.52%)最为常见,其次为BX2(18.1%)。结论OBI献血人群的KIR基因多态性具有自身特征,KIR 2DL3是OBI的潜在保护基因,KIR 2DS4*del则是OBI的潜在易感基因。     

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外周血CD4+CD25+FOXP3+调节性T细胞的检测和意义

目的检测系统性红斑狼疮（SEE）患者外周血CD4^＋CD25^＋FOXP3^＋调节性T细胞（Treg）的百分比，并分析其与疾病活动的相关性。方法采用流式细胞仪检测28例SLE患者（其中活动组18例）及22名正常对照组的外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比，同时评估SLE疾病活动指数（SLEDAI）及检测血抗dsDNA水平，分析相关性。结果SLE患者外周血CD4^＋CD25^＋FOXP3^＋Treg占CD4^＋T细胞的百分比较对照组降低（P〈0．05），以活动组尤为明显，CD4^＋CD25^＋FOXP3^＋Treg的百分比与SLEDAI呈明显的负相关（P〈0．01），同时显示血抗dsDNA阳性组较阴性组患者外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比显著下降（P〈0．01）。结论SLE患者外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比在活动期下降为明显，其在SLE的发病机制中可能起到重要的作用。     

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。     

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.     

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。     

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.     

系统性红斑狼疮患者外周血CD4^＋CD25^＋highCD127lowTreg和CD4^＋CD25^＋Treg水平测定及分析

目的观察系统性红斑狼疮（SLE）患者外周血CD4^＋CD25highCD127low调节性T细胞（Treg）和CD4^＋CD2^＋5Treg水平变化。方法用流式细胞术检测15例活动期SLE患者（SLE组）及20例健康查体者（对照组）外周血淋巴细胞亚群及CD4^＋CD25highCD127lowTreg、CD4^＋CD2^＋5Treg水平。结果 SLE组外周血中T细胞、B细胞及NK细胞比例与对照组比较无显著差异;SLE组外周血CD4^＋CD25highCD127lowTreg和CD4^＋CD2^＋5Treg水平均显著高于对照组（P〈0.05）。结论活动期SLE患者外周血中CD 4^＋CD25 highCD127 lowTreg和CD 4^＋CD 2^＋5 Treg水平显著升高;此是否与应用免疫抑制剂致患者发生自身免疫逃逸有关尚待进一步探讨。     

1型糖尿病患者外周血中CD4^＋CD25^＋与CD8^＋CD28^-调节性T细胞水平的研究

流式细胞仪检测1型糖尿病（T1DM）患者外周血CD4^＋CD25^＋与CD8^＋CD28^-调节性T细胞的水平,发现其外周血CD4^＋CD25^＋T淋巴细胞水平[（2．02±0．43）％]显著低于2型糖尿病（T2DM）组[（6．79±1．75）％]和健康对照（NC）组[（7．84±1．45）％],而CD8^＋CD28^-调节性T细胞水平三组间无差异。     

诱导缓解治疗对系统性红斑狼疮患者外周血CD4^＋CD25^＋T细胞表达的影响

目的探讨CD4^＋CD25^＋调节性T细胞在系统性红斑狼疮（SLE）患者诱导缓解治疗前后外周血的表达及其临床意义。方法入选28例SLE患者和15例正常对照者（对照组）。用流式细胞仪检测SLE患者和对照组的外周血CD4^＋CD25^＋T细胞阳性率。结果SLE患者在诱导缓解治疗前后CD4^＋CD25^＋调节性T细胞比率均低于对照组（P〈0．05）;诱导缓解治疗后患者外周血CD4^＋CD25^＋调节性T细胞比率较治疗前回升,两者间比较无统计学意义（P〉0．05）;SLE合并肾损害者CD4^＋CD25^＋T细胞比率显著低于未合并肾损害者（P〈0．05）。结论SLE患者外周血CD4^＋CD25^＋调节性T细胞数量显著低于正常人,合并肾损害者更明显,且CD4^＋CD25^＋T细胞比率和狼疮活动性指数之间存在相关性。诱导缓解治疗上调了患者外周血CD4^＋CD25^＋T细胞的数量。     

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 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.     

Association of killer cell immunoglobulin-like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus

To determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus. A total of 304 patients followed prospectively at the University of Toronto Lupus Clinic were assessed for the occurrence of vasculitis and vascular arterial events. Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping were performed. Chi-square and logistic regression were used to analyse association between KIR genes and vascular arterial events and aCL antibodies. In patients with vascular arterial events, there was a significant increase in KIR2DS2 (60% vs 45%, P = 0.02) and in KIR2DL2 (62% vs 47%, P = 0.01) compared with patients without events. There was no increase in activating KIR genotypes in patients with vasculitis. In patients with aCL antibodies, significant increases were seen in KIR2DS2 (54% vs 41%, P = 0.03) and KIR2DL2 (58% vs 41%, P = 0.003), but KIR2DL3 was decreased (87% vs 95%, P = 0.03). Logistic regression confirmed independent association of KIR2DS2 with vascular arterial events. We found an increase in KIR2DS2 in lupus patients with vascular arterial events, but not in patients with vasculitis.     

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 of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to ankylosing spondylitis

Objective

The killer cell immunoglobulin‐like receptors (KIRs) form a group of regulatory molecules that specifically recognize HLA class I molecules. The aim of this study was to analyze the possible contribution of the KIR3DL1 and KIR3DS1 alleles, in addition to HLA–B27, in the susceptibility to ankylosing spondylitis (AS) in a population of individuals from Spain.

Methods

We genotyped the KIR3DS1 and KIR3DL1 alleles in 2 cohorts of patients with AS and healthy control subjects. In total, 270 patients with AS and 435 healthy, HLA–B27–positive matched control subjects from Spain were enrolled. The KIR3DS1 and KIR3DL1 alleles were genotyped by sequence‐specific oligonucleotide probe–polymerase chain reaction, and their association with AS was analyzed. All individuals were typed for HLA–B.

Results

The KIR3DS1*013 allele was solely responsible for the increased frequency of the activator receptor KIR3DS1 in patients with AS compared with healthy HLA–B27–positive control subjects (35.7% versus 22.6% [P = 10⁻⁶], odds ratio 1.90, 95% confidence interval 1.50–2.40). The increased frequency of the KIR3DS1*013 allele in patients with AS was independent of the presence or absence of the HLA–Bw4I80 epitope. Moreover, the null allele KIR3DL1*004 was a unique inhibitory KIR3DL1 allele that showed a negative association with AS in the presence of HLA–Bw4I80.

Conclusion

The increased frequency of the KIR3DS1*013 allele in patients with AS is clearly independent of the presence of the HLA–Bw4I80 epitope, whereas the presence of inhibitory allotypes such as KIR3DL1*004 demonstrated a negative association in patients with AS in the presence of HLA–Bw4I80. As a consequence, the influence of KIR genotypes on AS susceptibility would be mediated by a general imbalance between protective/inhibitory and risk/activating allotypes.

     

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.     

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