HLA-A、B、DRB1等位基因多态性与中国南方鼻咽癌的相关性研究

目的：探讨南方人群中鼻咽癌（NPC）易感性与HLA多态性之间的关联。方法：应用聚合酶链反应／序列特异性引物（PCR-SSP）方法对35例NPC患者及60例正常对照进行HLA-A、HLA-B及DRBI基因分型。结果：NPC患者的HLA-A＊02、HLA-B＊58及HLA-DRBI＊03基因位点的频率高于正常对照组，HLA-B＊40基因位点的频率低于正常对照组。结论：HLA-A＊02、HLA—B＊58及HLA—DRB1＊03可能是NPC的易感性基因，HLA-B＊40可能是NPC的保护性基因。     

HLA与鼻咽癌相关性研究

目的探讨HLA抗原与鼻咽癌(NPC)病因学中发病风险的关系.方法用标准微量淋巴细胞毒性试验对30例NPC患者和25例正常人进行HLA-A、B、C抗原位点检测.结果HLA-A9(RR=2.636,P=0.05)、HLA-B27(RR=3.293,P=0.048)与NPC的发病风险呈正相关,而HLA-All(RR=0.29,P=0.02),与NPC的发病风险呈负相关.结论HLA-A9、A11、B27抗原与发生鼻咽癌的发病风险有着密切的关系.     

宫颈癌、卵巢癌与HLA的关联研究

目的探讨HLA抗原与宫颈癌、卵巢癌病因学中发病风险的关系.方法用标准微量淋巴细胞毒性试验对24例宫颈癌患者、22例卵巢癌患者和25例正常妇女进行HLA-A、B、C抗原位点检测.结果 HLA-B5(RR=3.459, P=0.037)与宫颈癌危险风险呈强的正相关,HLA-A11(RR=0.364, P=0.0556)与卵巢癌危险风险呈负相关.结论 HLA-B5抗原与宫颈癌,HLA-A11抗原与卵巢癌的发病风险有着密切的关系.     

HLA高分辨等位基因与骨髓移植受者HCMV抗原血症研究

目的 分析HLA高分辨等位基因与骨髓移植术后HCMVpp65抗原血症的相关性.方法 选取2009年2月至2010年10月在我院行骨髓移植术患者48例;采用免疫组化方法检测患者HCMVpp65,采用直接测序分型方法（PCR-SBT）检测患者HLA-A＊1101、HLA-A＊0201、HLA-A＊2402、HLA-B＊4001、HLA-DRB1＊0901五个高分辨等位基因.结果 ①48例骨髓移植术后患者HCMV感染率100％;②HLA-A＊1101、HLA-A＊0201、HLA-A＊2402、HLA-B＊ 4001等位基因阳性率在pp65抗原血症12例低感染组和36例高感染组中比较没有统计学意义（P＞0.05）,其阳性率HLA-A＊1101为33.3％ （8/24）和20.8％ （15/72）、HLA-A＊0201为4.2％ （1/24）和13.9％ （10/72）、HLA-A＊ 2402为12.5％ （3/24）和19.4％ （14/72）、HLA-B＊ 4001 16.7％ （4/24）和12.5％ （9/72）;③HLA-DRB1＊0901等位基因阳性率在pp65抗原血症12例低感染组和36例高感染组中比较有统计学意义（P =0.048）,其阳性率为4.2％ （1/24）和19.4％ （14/72）;④HLA-DRB1＊0901组患者pp65抗原血症高于HLA-A＊2402组（P =0.007）和HLA-A＊1101组患者（P=0.028）,HLA-A＊0201组患者pp65抗原血症高于HLA-A＊2402组患者（P=0.02）,其他高分辨等位基因组之间pp65抗原血症差异没有统计学意义（P＞0.05）.结论 HLA-DRB1＊0901等位基因可能与骨髓移植术后患者发生高HCMVpp65抗原血症有关;HLA-A＊2402等位基因可能与骨髓移植术后患者发生低HCMVpp65抗原血症有关.     

山东地区汉族人群中HLA-A、-B、-DRB1等位基因与原因不明卵巢早衰相关性研究

目的探讨HLA-A,-B和-DRB1位点等位基因多态性与原因不明卵巢早衰(premature ovarian failure,POF)的相关性。方法利用毛细管电泳测序技术(Capillary Electrophoresis),对36例汉族原因不明POF患者进行HLA-A,-B,-DRB1基因分型,并以865例山东健康汉族个体造血干细胞分型资料作为对照,分析HLA等位基因频率在两组中的分布差异。结果 POF组中HLA-A*33、HLA-B*07、HLA-B*52和HLA-B*55等位基因频率显著高于对照组(P<0.05)。HLA-A*33的等位基因频率POF组为19.44%,而正常对照组为10.17%,RR=2.18;HLA-B*07的等位基因频率POF组为12.50%,而正常对照组为5.32%,RR=2.65;HLA-B*52的等位基因频率POF组为11.11%,而正常对照组为4.10%,RR=3.06;HLA-B*55的等位基因频率POF组为5.56%,而正常对照组为1.50%,RR=4.23。结论山东汉族人群中HLA-A*33、HLA-B*07、HLA-B*52和HLA-B*55等位基因可能是POF的易感基因。     

加载白血病抗原肽PRl的HLA-A*0201四聚体制备

目的制备加载白血病抗原肽PR1的HLA-A＊0201四聚体。方法构建HLA-A＊0201-BSP和β2-微球蛋白（β2M）原核表达载体，进行目的蛋白表达、纯化。在体外将PR1（VLQELNVIV）与纯化的HLA-A＊0201-BSP、β2M通过稀释复性折叠成HLA-A＊0201-PR1复合物。利用BirA酶进行生物素标记。再经阴离子交换纯化得到生物素化的HLA-A＊0201-PR1复合物单体。此单体与PE标记的链霉亲和素按4：1比例混合，即可形成四聚体。结果成功制备了HLA-A＊0201-PRl四聚体。结论制备的HLA-A＊0201-PR1四聚体为定量检测白血病患者体内PR1抗原特异性的细胞毒性T淋巴细胞提供了有力工具。     

强直性脊柱炎患者MICA基因第2、3和4外显子的多态性及其与HLA-B抗原的连锁不平衡

目的探讨皖籍汉族人群MICA基因（major histocompatibility complex class Ⅰchain-related gene A，MICA）第2、3、4外显子的多态性，及其与HLA-B抗原的连锁不平衡在强直性脊柱炎（ankylosing spondylitis，AS）发病中的作用。方法采用聚合酶链反应-序列特异性寡核苷酸探针杂交（polymerase chain reactionsequence-specific oligonucleotide probing，PCR-SS0）技术对56例AS患者和112名正常对照人群进行MICA基因第2、3、4外显子的多态性和HLA-B抗原的检测。结果AS患者和正常对照人群的MICA等位基因分布均以MICA＊008占优势，频率分别为32．14％和30．36％。两组人群MICA＊007等位基因的分布差异有统计学意义（X^2=10．18，P〈0．05，RR=2．50）。单倍型分析显示，AS患者和正常对照人群的MICA等位基因均显示出与多个HLA-B位点的连锁不平衡现象，两组间差异有统计学意义的单倍型为MICA＊007-B27（X^2=18．46，P〈0．05，RR=7．47）。分层分析结果显示，HLA-B27阳性与AS的相关性有统计学意义（P〈0．05），但MICA＊007基因与AS的相关性无统计学意义（P〉0．05）。结论AS患者中MICA＊007等位基因频率的显著升高可能源于MICA基因与HLA-B位点间的广泛连锁不平衡。     

中国甘肃地区汉族白血病易感性与HLA-Ⅰ类抗原之间的相关性

目的：探讨中国甘肃地区汉族白血病易感性与HLA-Ⅰ抗原之间的相关性，找出白血病的易感基因。方法：采用特异性寡核苷酸探针杂交(PCR/SSO)法，初步对43名白血病病人和66名健康对照进行了HEA-Ⅰ抗原分型。结果：经过SSPS10．0统计软件分析，中国甘肃地区汉族白血病患者HLA-A’01和HLA-A‘11基因的统计结果分别为x^2=6．350，P=0．028、X^2=5．574，P=0．018。显示相关性。结论：中国甘肃地区汉族人群中HLA-A01和HLA-A’11与白血病有相关性。     

同种T细胞前体频率与MHC-抗原肽种类呈正相关

目的用种类数目不同的肽段加载T2（表达空载HLA-A2分子）细胞与HLA-A2阴性个体的PBL混合培养，探讨同种反应性CIL前体的频率与同种抗原表位种类多少的关系。方法通过人工合成HLA-A2限制性单一病毒抗原肽、10种细胞正常成分的肽段以及冻融酸处理法制备细胞混合肽。加载T2细胞，经丝裂霉素灭活后作为刺激细胞，与PKH67预染HLA-A2阴性个体PBL进行混合淋巴细胞培养，PKH67荧光强度随细胞增殖而递减，通过流式细胞仪增殖软件（ModFit）分析同种T细胞前体频率。结果单独PBL增殖不明显；空载T2细胞刺激同种反应性CTL前体的频率为0．052819；加载单一表位肽的T2细胞刺激时，前体的频率为0．030429；10种HLA-A2自身限制性的混合抗原肽负载时，前体的频率为0．144942；混合多肽负载时，前体的频率为0．203649。结论本研究结果显示了同种T细胞前体的频率随着同种抗原表位种类的增多而增高，与同种抗原的密度不相关；支持了强烈的同种反应的主要原因是同种细胞表面表达极其繁多的T细胞识别表位（即pMHC）。     

鼻咽癌患者血清TGF-β1、IL-8水平和T淋巴细胞亚群水平测定的临床意义

目的：探讨了鼻咽癌患者血清TGF-β1、IL-8和T淋巴细胞亚群水平的变化及意义。方法：分别应用放免法、酶联免疫法和单克隆抗体测定对31例鼻咽癌患者进行了血清TGF-β1、IL-8水平和T淋巴细胞亚群的测定,并与35例正常健康人作比较。结果：鼻咽癌患者血清TGF-β1、IL-8和CD8水平非常显著高于正常人组（P〈0．01）,而CD3、CD4、CD4／CD8比值又非常显著低于正常人组（P〈0．01）。鼻咽癌患者血清TGF-β1水平和CD4细胞数量及与CD4／CD8比值呈负相关,与CD8细胞呈正相关。结论：观察鼻咽癌患者血清TGF-β1、IL-8水平和T淋巴细胞亚群水平的改变有助于鼻咽癌的诊断及对预后的评价。     

Primary biliary cirrhosis associated with HLA-DRw3

Twenty-one unrelated Caucasian patients with Primary Biliary Cirrhosis were typed for HLA-A, B, C and HLA-DRw antigens. The antigens HLA-Al, HLA-B8 and HLA-DRw3 were found in increased frequency in relation to the control group. When the P values were corrected for the number of antigens tested only the increase of HLA-DRw3 remained significantly different from the control group (P crr. < 0.004). The antigen HLA-DRw3 was carried by 12 out of 21 patients (57.1%) in comparison to 11 out of 74 (14.8%) normal unrelated Caucasian subjects.     

湖南地区鼻咽癌MHC-Ⅰ类链相关基因A第5外显子微卫星多态性研究

目的研究MHC-Ⅰ类链相关基因A(MHC class-Ⅰ chain related gene A, MICA)第5外显子微卫星多态性与湖南地区鼻咽癌之间的相关性.方法应用荧光聚合酶链反应-基因扫描技术和聚合酶链反应-序列特异性引物技术分析127例湖南地区鼻咽癌患者和112名正常人群MICA基因第5外显子微卫星等位基因及MICA基因缺失(MICA*Del)频率.结果 MICA*A9表型频率在患者组(45/127)高于对照组(20/112),相对风险值(relative risk)为2.524(P=0.001,Pc=0.006);MICA*A5.1表型频率在患者组(51/127)低于对照组(69 /112),相对风险值为0.418(P=0.0004, Pc=0.0026).进一步分析发现,MICA*A9在男性患者组的表型频率(35/101)高于男性对照组(11/78),相对风险值为3.23(P=0.00095,Pc=0.006);MICA*A5.1在男性患者组的表型频率(39 /101)低于男性对照组(49/78),相对风险值为0.372 (P=0.0007,Pc=0.004);各MICA-STR 等位基因频率在女性患者组与女性对照组之间的差异无统计学意义(Pc＞0.05).结论湖南地区MICA-STR等位基因多态性与鼻咽癌相关,MICA*A9是该人群男性个体的一个鼻咽癌遗传易感标记.     

HLA Antigens and Susceptibility to Psoriasis Vulgaris in a Non-Caucasian Population

Fifty-four unrelated Japanese patients with psoriasis vulgaris were tissue typed using the Sixth International Histocompatibility Workshop antisera. Two control groups were included in this study: Thirty-one pustulosis palmaris et plantaris and 17 seborrheic dermatitis as a disease control and 66 normal, healthy, unrelated Japanses as a reference. HLA-Al (P = 0.0065) from the A locus and HLA-BW37 (P = 0.0164) from the B locus were found to occur with increased frequency in patients with psoriasis vulgaris. No significant difference in antigen frequencies in pustulosis palmaris et plantaris was found, however, HLA-AW30 and/or AW31 and HLA-B12 occurred with increased frequency in seborrheic dermatitis. No linkage between psoriasis and HLA was observed in eight families. Therefore our findings in Japanese do not confirm the previous observation made in Caucasians of an association between psoriasis vulgaris and HLA-B13 or BW17.     

湖南地区白血病MHC-Ⅰ类链相关基因A微卫星多态性分析

目的:探讨MHC-Ⅰ类相关链基因A(MHC class-Ⅰchain related gene A,MICA)与湖南地区白血病之间的相关性。方法:应用荧光聚合酶链反应-基因扫描技术和聚合酶链反应-序列特异性引物技术分析,对62例白血病患者和112名正常人群进行MICA基因第5外显子微卫星等位基因分型及MICA基因缺失检测。结果:慢性粒细胞白血病组(n=35)的MICA*A5基因频率显著低于正常对照组(RR=0.635,P=0.0380);急性淋巴细胞性白血病组(n=13)的MICA*A4基因频率显著低于正常对照组(RR=0.120,P=0.0297);而在急性非淋巴细胞性白血病组(n=14),MICA*A5基因频率显著高于正常对照组(RR=2.229,P=0.0218)。结论:本文数据显示,MICA-STR多态性与湖南地区白血病之间存在相关性;不同病理类型的白血病相关格局有所不同。     

人类白细胞抗原DRB1等位基因与乙肝后肝硬化遗传易感性的研究

目的 研究人类白细胞抗原(human leucocyte antigen，HLA)-DRBl等位基因多态性与湖北汉族乙肝后肝硬化遗传异感性的关系，为寻找乙肝后肝硬化的易感基因或抗病基因提供线索。方法 应用聚合酶链反应-序列特异性引物技术对106例湖北汉族乙肝后肝硬化患者和108名正常健康对照者进行了HLA-DRBl等位基因检测，并结合临床资料进行比较分析。结果 乙肝后肝硬化组HLA-DRBl*1201／1202等位基因频率明显升高(20．28％vs6．01％，RR＝4．9878，P＜0．001)，HLA-DRBl*1501／1502等位基因频率明显下降(16．67％vs6．6％，RR＝0．3043，P＜0．05)，其他等位基因在两组之间差异无显著性。结论 HLA-DRBl*1201／1202等位基因可能是湖北地区汉族人群乙肝后肝硬化的易感基因，HLA-DRB1*1501／1502则为抵抗基因。     

HLA-B*51 allele analysis by the PCR-SBT method and a strong association of HLA-B*5101 with Japanese patients with Behçet's disease

Abstract: Behçet's disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA-B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101–B*5121. Further, not only HLA-B*5101 but also HLA-B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. Ninety-six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; P c=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51-positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51-positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA-B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA-B*5101 allele.     

Study on the association of HLA with malignant lymphoma

The association of HLA with malignant lymphomas in 50 Chinese patients of the HAN nationality was investigated. The frequencies of antigens HLA-A and -C and the majority of HLA-B phenotypes were not significantly different between the patient and control groups, whereas the antigen frequency of HLA-B16 was increased significantly (P less than 0.025) in the patient group. The relative risk associated with HLA-B16 was 2.5694. The association of this antigen with malignant lymphoma might be unique for Oriental patients.     

HLA and Gm genes in systemic lupus erythematosus

HLA and Gm phenotypes were compared in 53 patients with unequivocal systemic lupus erythematosus (SLE) and in 180 healthy subjects. SLE was associated with HLA-B8 (relative risk (RR) = 3.5, P less than 0.001) and with HLA-DR3 (RR = 2.8, P less than 0.01). There was an increased risk of SLE with HLA-B8/B27 (RR = 27.6) and with HLA-B15/B35 (RR greater than 13) and, in contrast, the risk was decreased in subjects with HLA-B40 (RR = 0.3). The risk of SLE in subjects who were heterozygous for the Gm phenotypes a,f,x; b,g was increased (RR = 2.0, P = 0.03) relative to the risk in subjects who were homozygous for these Gm phenotypes. These findings suggest that susceptibility to SLE is influenced by one or more genes in linkage disequilibrium with the HLA-B8-DR3 haplotype, by "augmentor" or "protector" genes associated with other HLA antigens and by separate genes, possibly VH genes, in linkage disequilibrium with the Gm (CH allotype) locus.