岳阳地区汉族人群HLA-A、-B、-DRB1高分辨等位基因多态性研究

目的研究岳阳地区汉族人群HLA-A、B、DRB1等位基因多态性的分布特征。方法应用聚合酶链反应-直接测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)高分辨技术,对岳阳地区3 560名无血缘关系的汉族人群HLA-A、-B、-DRB1进行基因分型。结果检出HLA-A、-B、-DRB1等位基因分别有53、89、53种,经统计分析这3个基因座分布均符合Hardy-Weinberg平衡定律。A*0207-B*4601-DRB1*0901和A*3303-B*5801-DRB1*0301单体型是岳阳地区汉族人群最常见单体型。结论岳阳地区汉族人群HLA-A、-B、-DRB1基因分布具有高度的遗传多态性并有其自身分布特点,中国各地常见的基因及罕见基因均有分布。     

一个蒙古族人群HLA-A位点DNA多态性分析

目的人类白细胞抗原(Human Leucocyte Antigen,HLA)编码基因具有高度遗传多态性,有关中国人群HLA分布,已有的文献报道主要为汉族人群数据。本工作首次采用DNA分型技术,分析蒙古族HLA-A位点多态性。方法采用ARMS/PCR技术对83例居住在内蒙古地区的蒙古族健康个体做HLA-A DNA分型。结果该人群存在HLA-A*01至A*33等11种等位基因(组),其中,以HLA-A*02频率最高(0.2886),HLA-A*11、A*24次之;该人群中,HLA-A19宽特异性(Broad Specificity)含有HLA-A*29、A*30、A*31、A*32、A*33等5组编码基因,频率之和为0.2368;此外,在蒙古族,HLA-A*01较为常见(基因频率为0.08823)。结论本研究在DNA水平提供了蒙古族HLA-A位点频率分布数据。     

山西骨髓分库4000例造血干细胞捐献志愿者HLA-A、B、DRB1基因多态性和单倍型研究

目的分析中国造血干细胞捐献者资料库山西省分库(以下简称山西分库)人群中HLA-A、B、DRB1基因多态性和单倍型的分布特征。方法采用PCR-SSO和SBT基因分型技术对山西分库4 000例无关志愿者做HLA-A、B、DRB1高分辨基因分型,以直接计数法计算等位基因频率,采用最大数学预期值算法、应用Arlequin 3.01软件分析单倍型频率。结果山西分库志愿者HLA抗原频率分布符合Hardy-Weinberg平衡,共检出HLA-A位点等位基因48个,B位点等位基因97个,DRB1位点等位基因52个;A位点频率最高的是A*02∶01(17.8%),B位点频率最高的是B*51∶01(8.3%),DRB1位点频率最高的是DRB1*15∶01(12.6%);频率最高的HLA-A、B、DRB1单倍型是A*30∶01-B*13∶02-DRB1*07∶01(3.1%)。结论分析山西分库志愿者人群HLA基因频率分布,有助于指导临床寻找HLA匹配的无关供者,为HLA与疾病相关研究和中国人群群体遗传学研究等提供了有意义的基础性资料。     

PCR-SSP技术应用于海南汉族HLA-A、B、DRB1基因多态性研究

[目的]研究海南汉族HLA-A、B、DRB1基因多态性.分析该群体HLA等位基因分布特点.[方法]应用顺序引物聚合酶链反应技术对3 140名海南汉族健康、无血缘关系的捐献造血干细胞血样者进行HLA-A、B、DRB1基因分型检测,并与其他汉族群体进行比较.[结果]检出A等位基因17个,B等位基因28个,DRB1等位基因13个.其中HLA-A*11(0.355 3)、A*02(0.287 3)、A*24(0.194 6)、A*33(0.104 5)、HLA-B*40(0.189 6)、B*15(0.152 6)、B*13(0.145 1)、B*46(0.128 5)、B*58(0.101 8)、HLA-DRB1*15(0.164 9)、DRB1*12(0.141 4)、DRB1*04(0.133 6)、DRB1*09(0.128 7)等位基因具有较高的基因频率.[结论]海南汉族HLA等位基因多态性具有南方汉族人群共同的特征,但可能受北方汉族的影响,具有自身的特点.     

岳阳地区血小板志愿捐献者HLA、HPA基因库的建立及临床意义

目的：建立岳阳地区人类白细胞抗原（HLA）、血小板特异性抗原（HPA）已知基因型血小板供者资料库,为临床血小板输注无效的患者提供有效的输血治疗。方法：对岳阳地区303例无血缘关系的血小板捐献者血样分别采用PCR-NGS、PCR-SSP方法对HLA-A、B、C位点及HPA-1～6、15、21系统进行基因分型,计算其基因频率和基因型频率。结果：HLA-A抗原共检出15个,基因频率最高的是A*11(0.3069),A*02(0.2871),A*24(0.2145);HLA-B抗原共检出27个,基因频率最高的是B*40(0.2393),B*46(0.1666),B*15(0.1419),B*13(0.0809),HLA-C抗原共检出15个,基因频率最高的是C*07(0.2261),C*01(0.2244),C*03(0.2096),C*08(0.1320)。HPA-1-6,15,21系统抗原具有多态性,杂合度最高的是HPA-15,其aa、ab、bb基因频率分别为0.1947、0.4951、0.3102;其次是HPA-3,基因频率分别是0.3927、0.4389、0.1683。不配合率最高的基因...     

湖南地区人群HLA-A、B、DRB1等位基因多态性的研究

目的研究湖南地区人群HLA-A、B、DRB1位点等位基因的多态性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)技术对3 664名湖南籍健康人进行HLA-A、B、DRB1等位基因的低分辨分型。结果本次研究共检出HLA-A、B、DRB1位点等位基因74种,其中A位点17种,B位点44种,DRB1位点13种。A位点中A*11(34.42%)、A*02(31.88%)、A*24(18.01%)、A*33(6.18%)为湖南人群的优势基因。B位点中B*40(23.70%)>B*46(17.76%)>B*15(13.99%)>B*13(8.60%)。DRB1位点中,频率最高的为DRB1*09(19.69%),其次为DRB1*15(14.01%)、DRB1*12(12.97%)、DRB1*04(11.96%)、DRB1*08(9.02%),频率最低的为DRB1*01(0.88%)。与其他地区不同人群相比,HLA-A、B、DRB1各位点等位基因的分布均有显著的差异。结论湖南人群的HLA-A、B、DRB1位点等位基因具有复杂的多态性,中国各地常见的基因均有分布,白血病患者在湖南不难找到合适的造血干细胞供者。本研究结果可作为湖南地区人群正常参考值,为人类学及HLA与疾病相关的研究提供了有力的背景资料。     

海南黎族人群HLA-A、B、DRB1基因分型

[目的]研究海南黎族人群HLA-A、B、DRB1遗传特征.[方法]应用顺序引物聚合酶链反应技术对301名海南黎族健康、无血缘关系的捐献造血干细胞血样者进行HLA-A、B、DRB1基因分型检测,并与南北汉族、其他少数民族群体进行比较.[结果]检出HLA-A等位基因11个,B等位基因20个,DRB1等位基因13个,其中A、B、DRB1座位频率最高的等位基固依次是:HLA-A*11(O.3634)、A*02(O.2507)、A*33(0.1767)、A*24(O.1451)、HLA-B*58(0.1972)、B*13(0.1788)、B*40(0.1278)、B*46(0.1259)、HLA-DRB1*03(0.1808)、DRB1*15(0.1667)、DRB1*16(0.1627)、DRB1*09(0.1240).[结论]海南黎族在HLA分布上属于南方民族类型,与西南少数民族壮族、布依族、傣族具有相似的遗传基因背景,并且在长期进化中形成自己的优势基因.     

老年慢性病患者肺部感染与CD14及HLA基因多态性的关系

目的分析老年慢性病患者肺部感染与白细胞分化抗原14(CD14)和人类白细胞抗原(HLA)基因多态性的关系。方法选取2017年10月-2019年10月菏泽市单县中心医院老年慢性疾病患者615例,以其中合并肺部感染者97例(15.77%)为研究组,另在未合并肺部感染者中随机抽取92例为对照组,采集两组临床资料,检测并比较两组CD14-159 C/T、CD14-260 C/T和HLA-A、HLA-B和HLA-DRB1基因分布。结果两组患者性别、年龄、体质量指数(BMI)及基础疾病等临床资料比较差异无统计学意义,研究组合并慢性疾病种类较对照组多(P<0.05);两组CD14-159 C/T基因型分布差异显著(P<0.05),研究组CD14-159 C等位基因频率显著低于对照组,T等位基因频率显著高于对照组(P<0.05),两组CD14-260 C/T基因型及等位基因频率比较差异无统计学意义;研究组HLA-A*0101等位基因频率高于对照组,HLA-B*5201和HLA-DRB1*1502等位基因频率低于对照组,差异有统计学意义(P<0.05)。结论合并慢性疾病种类较多的老年慢性疾病患者容易发生肺部感染,感染可能与CD14和HLA基因多态性有关,CD14-159 TT和HLA-A*0101可能为易感基因。     

人巨细胞病毒临床株US3基因HLA-A*0201限制性CTL表位预测

目的分析晚期黄疸新生儿人巨细胞病毒(HCMV)感染患儿临床株US3基因序列,预测HCMV US3基因HLA-A*0201限制性CTL表位。方法应用巢式PCR法检测20例HCMV感染新生儿标本US3基因,结果进行双向DNA测序。SYFPEITHI和NetCTL方案预测HCMV临床株US3基因HLA-A*0201限制性CTL表位。结果①以Towne作为参考株,序列比对分析显示,20株临床分离株US3的ORF长度均与参考株相同,为561 bp,编码186个氨基酸蛋白。US3氨基酸序列高度保守,仅几个位点在少数分离株中存在变异,变异主要集中在序列的N端,大部分是同义突变。②通过预测获得5个HCMV US3基因HLA-A*0201限制性CTL表位:FTEKHFVSV、RMDYSSQTI、RMDYSSHTI、SIRDDNWGL和SMRDDNWGL。不同临床株US3基因HLA-A*0201限制性CTL表位存在差异。结论初步筛选出人巨细胞病毒临床株US3基因HLA-A*0201限制性CTL表位,为进一步研究HCMV感染的免疫机制提供实验依据。     

献血人群丙型肝炎病毒感染与人类白细胞抗原A基因的相关性

目的探讨浙江献血人群中丙型肝炎病毒感染与人类白细胞抗原A基因的相关性。方法选择2011年10月-2013年10月浙江省血液中心献血人群,经血液核酸筛查HCV RNA阳性的样本45例。采用基因测序方法检测HLA-I类基因中A等位基因情况,同时以健康人8 333例为对照样本。结果 HLA-A基因的A*02∶01(P=0.002 9,OR=2.18,95%CI:1.32~3.59)和A*33∶01(P=0.0270,OR=26.74,95%CI:3.25~219.7)位点在HCV RNA阳性献血者中的频率与健康对照人群比较差异有统计学意义。结论在浙江献血人群中HCV感染与HLA-A基因中部分多态性位点有相关性。     

山东省汉族人群慢性肾小球肾炎与人白细胞抗原相关性研究

目的探讨慢性肾小球肾炎（CGN）与人白细胞抗原（HLA）的相关性。方法以山东省3所省级医院近十年汉族CGN尿毒症患者1073例为病例组，选择中国造血干细胞捐献者资料库山东省分库汉族人7418名无关汉族健康志愿捐献者为对照组，对两组的HLA-I、Ⅱ类A、B、DRBl三个位点的基因多态性进行分析比较，探寻上述基因多态性与CGN的关系；并随访了部分携带易感基因的患者，评价其预后。结果病例组中HLA-A23、A25、B15、B40、B53、DRBl＊18基因频率显著高于对照组，这些基因可能是CGN尿毒症的易感基因，且随访发现携带该类基因的患者预后较差。病例组中A23-t344．DRBl＊18、A25-B15-DRBl＊07、A3-B70-DRBl＊11、A68．B13-DRBl＊04、A11-B10-DRBl＊12五个单倍型基因频率显著高于对照组，同时检出HLA-A20、A22、A35、A36、A38、B21、B73、B78等8种低频率基因在对照组中未见表达；病例组中HLA-A32、A33、B50、B58、B60、B71、DRBl＊16基因频率显著低于正常对照，这些基因可能是慢性肾小球肾炎尿毒症的保护基因。结论山东省汉族人群CGN与HLA具有较强关联性，且携带可能易感基因的患者肾移植预后较差。     

HLA-Ⅰ等位基因对HIV-1特异性细胞毒性T细胞免疫应答的影响

目的 探讨中国人群HLA-Ⅰ等位基因对HIV-1抗原特异性CTL免疫应答的影响.方法 采用酶联免疫斑点(ELISPOT)技术,以HIV-1 P24区域的12个重叠肽段作为特异性肽段表位,刺激100例HIV-1感染者的外周血单核细胞(PBMC),检测IFN-γ分泌细胞频率;并用PCR特异性引物扩增法测定上述研究对象的HL...     

HLA-DRB1* and DQB1* allele and haplotype diversity in eight tribal populations: Global affinities and genetic basis of diseases in South India

The distribution of HLA class-II DRB1* and DQB1* alleles/ haplotypes were studied in 438 individuals of 8 Dravidian tribal groups inhabiting the Western Ghats, south India. The HLA typing was performed by PCR-SSP method. In order to identify the 5-locus Ancestral Extended Haplotypes (AEH), the alleles of HLA-A, -B and -C loci were typed for DNAs with predominant 2-locus haplotypes. The analyses have revealed allele HLA-DRB1*15 as the most predominant allele (Lowest / Highest range: Urali, 14.81 / Malasar, 48.94), followed by the alleles DRB1*10 (Katunayakan, 1.85 / Paliyan, 48.21), DRB1*14 (Paliyan 4.46 / Katunayakan, 40.74), DRB1*12 (Mannan, 1.64 / Katunayakan, 20.37) and DRB1*03 (Mannan, 1.64 / Urali, 29.63). The most frequent DQB1* alleles were DQB1*02 (Paliyan 3.57 / Urali, 23.15), DQB1*05 (Katunayakan, 27.77 / Paliyan 84.82) and DQB1*06 (Malasar, 8.51 / Kuruman, 33.51). The most predominant two-locus haplotypes observed were DRB1*15-DQB1*05, DRB1*10-DQB1*05, DRB1*15-DQB1*06 and DRB1*04-DQB1*05. The present study of HLA immunogenetics of south Indian tribes have revealed the presence of globally shared two and 5-locus haplotypes. Many of these haplotypes were implicated in a number of diseases in south India. We observed the presence of ancestral extended haplotypes (AEHs), hitherto not reported in Indian populations such as, A*68-B*35-C*02-DRB1*15:01-DQB1*05:01, A*24-B*57-C*06-DRB1*04:01-DQB1*05:01 and A*24-B*35-C*02-DRB1*15:01-DQB1*05:02. The dendrogram based phylogenetic analyses have revealed the Caucasian affinity of Urali, palaeo-Mediterranean and Indo-European affinity of Malasar tribes. The presence of globally shared susceptible and protective haplotypes reiterated the mosaic immunogenetic fabric of south Indian tribes.     

HLA and response to booster hepatitis B vaccination in anti-HBs-seronegative adolescents who had received primary infantile vaccination

To explore contemporarily genetic and non-genetic determinants of long-term immunological memory to hepatitis B (HB) vaccination, we conducted a case-control study nested in an adolescent cohort of booster recipients who had received primary infantile HB vaccination but with residual anti-HBs titers <10 mIU/mL at 15-18 years of age. High-resolution phenotypes of human leukocyte antigen (HLA)-A, -B, and -DRB1 loci were determined by sequence-specific oligonucleotide probe hybridization. After controlling for pre-booster anti-HBs levels, the absences of HLA-A*02 and -DRB1*08, simply expressed as A*02(-) and -DRB1*08(-), and the presence of B*15 were significantly associated with elevated risks of non-response (post-booster anti-HBs titers<10 mIU/mL) to booster vaccination. The adjusted odds ratios (ORs) were 3.85 (CI, 1.82-8.33), 4.55 (CI, 1.23-16.67), 3.59 (CI, 1.40-9.17), respectively. There was multiplicative synergism between A*02 and B*15 on the risk of non-response to booster vaccination. The multivariate-adjusted ORs for A*02(-)/B*15, A*02(-)/B*15(-), A*02/B*15, and A*02/B*15(-) haplotypes were 20.39 (p=0.0003), 3.29 (p=0.007), 1.32 (p>0.05), and 1.0, respectively. Recent cigarette smoking and/or betel-quid chewing was associated with a 12-fold risk of non-response to booster vaccination. Further comparisons between responders and adolescents who had undetectable post-booster anti-HBs titers (<0.1 mIU/mL) demonstrated similar results. Our results indicated that response to booster HB vaccination as well as long-term immunological responses to HB vaccination are closely related with host genetic factors, and probably modified by recent substance use.     

Significant association of acute lymphoblastic leukemia with HLA-Cw7

Frequencies of all defined HLA-A, -B, -C (-DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age-related subgroups of the disease. A highly significant rise of the HLA-C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA-Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age-related patient groups. HLA-A, -B, or -DR antigens, as well as HLA-ABC three-locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA-linked genetic factors conferring susceptibility to ALL in adults, particularly those presenting with B-, T-, and Null-ALL.     

Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín,Colombia

The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy of HIV-infected patients; nevertheless, it does not eliminate the virus from hosts, so a cure for this infection is crucial. Some strategies have employed the induction of anti-HIV CD8⁺ T cells. However, the high genetic variability of HIV-1 represents the biggest obstacle for these strategies, since immune escape mutations within epitopes restricted by Human Leukocyte Antigen class I molecules (HLA-I) abrogate the antiviral activity of these cells. We used a bioinformatics pipeline for the determination of such mutations, based on selection pressure and docking/refinement analyses. Fifty HIV-1 infected patients were recruited; HLA-A and HLA-B alleles were typified using sequence-specific oligonucleotide approach, and viral RNA was extracted for the amplification of HIV-1 gag, which was bulk sequenced and aligned to perform selection pressure analysis, using Single Likelihood Ancestor Counting (SLAC) and Fast Unconstrained Bayesian Approximation (FUBAR) algorithms. Positively selected sites were mapped into HLA-I-specific epitopes, and both mutated and wild type epitopes were modelled using PEP-FOLD. Molecular docking and refinement assays were carried out using AutoDock Vina 4 and FlexPepDock. Five positively selected sites were found: S54 at HLA-A*02 GC9, T84 at HLA-A*02 SL9, S125 at HLA-B*35 HY9, S173 at HLA-A*02/B*57 KS12 and I223 at HLA-B*35 HA9. Although some mutations have been previously described as immune escape mutations, the majority of them have not been reported. Molecular docking/refinement analysis showed that one combination of mutations at GC9, one at SL9, and eight at HY9 epitopes could act as immune escape mutations. Moreover, HLA-A*02-positive patients harbouring mutations at KS12, and HLA-B*35-positive patients with mutations at HY9 have significantly higher plasma viral loads than patients lacking such mutations. Thus, HLA-A and -B alleles could be shaping the genetic diversity of HIV-1 through the selection of potential immune escape mutations.     

Identification of novel HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from Zinc Transporter 8

Numerous evidences demonstrated that type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8⁺ T cells play an important role in the development of T1D. Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D. However, ZnT8-associated CTL specific-peptides have not been identified. In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice. The results demonstrated that peptides of ZnT8 containing residues 107–115, 115–123 and 145–153 could elicit specific CTLs in vitro, and induce diabetes in mice. The results suggest that these specific peptides are novel HLA-A*0201-restricted CTL epitopes, and could have therapeutic potential in preventing of T1D disease.     

HLA antigen frequencies in flax byssinosis patients.

Not all workers exposed to flax dust contract byssinosis. It is not known what determines susceptibility or insusceptibility. This study is an attempt to establish whether the incidence of histocompatibility antigens is involved in susceptibility to the disease. Forty patients suffering from flax byssinosis were tissue-typed for HLA-A and -B antigens. HLA-B27 was significantly more common in the patients (22.5%) than in the controls (5.5%); P = 0.029 after correction for the number of antigens compared. HLA-A11 was present in twelve patients (30%) compared with 14% in the controls; after correction for the number of comparisons, this is not a statistically significant increase. Because HLA-B27, though significantly more common in flax byssinosis, is not necessary for its occurrence (77.5% of our patients did not have it), it is possible that the increase in the frequency of HLA-B27 is attributable to an association with other genes, perhaps those regulating the immune response or coding for antigens at other HLA loci.