鼻咽癌高发家系中的HLA—[A2—B46]单倍型

应用连锁分析法检测了６个鼻咽高发家系中ＨＬ－Ａ［Ａ－Ｂ］单倍型。其中４个家系鼻咽癌患者１８人，接受检查１０人，均属ＨＬＡ－Ａ－［Ａ２－Ｂ４６］单倍型，即Ａ２和Ｂ４６在同一条染色体上，在一个大家系统，第Ⅱ，Ⅲ两代血缘亲属２１个中有患者１１人，受检５人均具ＨＬＡ－［Ａ２－Ｂ４６］单倍型。其中２人在确定此单倍型后半年和１１个月才发生鼻咽癌，故认为ＨＬＡ－［Ａ２－Ｂ４６］可能与鼻咽癌发生相关。通过家系ＨＬ     

HLA多态性在广东汉族人群分布的特殊性

目的探讨人类白细胞抗原（ｈｕｍａｎｌｅｕｃｏｃｙｔｅａｎｔｉｇｅｎＨＬＡ）在广东汉族群体中的遗传特征。方法采用免疫磁珠单抗血清学技术进行ＨＬＡ－Ａ、Ｂ分型和聚合酶联反应－序列特异性引物（ｓｅｑｕｅｎｃｅｓｐｅｃｉｆｉｃｐｒｉｍｅｒｓＰＣＲ－ＳＳＰ）进行ＨＬＡ－ＤＲ、ＤＱ分型,调查了４０６名广东汉族健康献血员。结果识别ＨＬＡ－Ａ、Ｂ、ＤＲ和ＤＱ座位１０６个特异性,４１４２条单倍型,发现ＨＬＡ－Ａ３３－Ｂ５８－ＤＲ１７－ＤＱ２和ＨＬＡ－Ａ２－Ｂ４６－ＤＲ９－ＤＱ９在广东汉族中呈现高频率。结论ＨＬＡ－Ａ３３－Ｂ５８－ＤＲ１７－ＤＱ２和ＨＬＡ－Ａ２－Ｂ４６－ＤＲ９－ＤＱ９,这两条单倍型在广东汉族人群中的分布频率与相关文献其他民族和人群相比为显著连锁不平衡单倍型。     

用DNA分型研究中国人HLA-A,-C,-B的部分单倍型

目的对ＨＬＡ－Ⅰ类基因同时进行ＤＮＡ基因分型和血清学分型,比较血清学分型的误差及改良的可能性;实测我国华东地区１个相对隔离人群的ＨＬＡ－Ａ－Ｃ－Ｂ单倍型的种类和特点,评估它们的意义。方法对安徽省一个相对隔离人群的两个大家系三代１４个小家庭中共８３人用血清学分型和ＤＮＡ基因分型两种方法进行ＨＬＡ－Ａ－Ｃ－Ｂ三座位的分型。根据遗传分离定律演绎出它们的单倍型并进行分析。结果发现血清学方法的总误差率达１７．２％;但我们认为血清学分型仍有相当大的改进余地。基因分型共检出ＨＬＡ－Ａ基因１２种,Ｂ基因１９种,Ｃ基因１１种;三座位单倍型共３５种;发现ＨＬＡ－Ｂ－Ｃ之间的连锁不平衡远大于Ａ－Ｃ之间;分析判定了３种祖先单倍型;指出遗传漂变的存在对本人群单倍型的非随机性有重要的影响。结论使用本文的研究方法以及获得的结果可为不同地区隔离人群的同类研究提供经验和进行比较     

华北汉族人群HLA单倍型研究

对北京附近河北省固安县地区的１０３个多子女家庭进行了ＨＬＡ－Ａ、Ｂ、Ｃ、ＤＲ、Ｂｆ、Ｃ２、Ｃ４Ａ、和Ｃ４Ｂ等八个位点的等位基因的分型，分析了八个位点的ＨＬＡ扩展单倍型，揭示出中国华北地区汉族人群ＨＬＡ单倍型的面貌。研究证明ＨＬＡ单倍型各位点间的等位基因呈高度的连锁不平衡，并显示出中国人不同于其他人种的特点。同时讨论了ＨＬＡ单倍型分析的重要意义。     

HLA多态性与HIV感染及AIDS发病相关性的研究

为研究人类白细胞抗原（ＨＬＡ）和人免疫缺陷病毒（ＨＩＶ）易感性的关系，本文分析比较了以下三组人群的ＨＬＡ表型频率和单倍型频率：①１７２例正常人；②１７例血清ＨＩＶ阴性高危人群；③１８０例血清ＨＩＶ阳性患者，其中２１例发展为艾滋病（ＡＩＤＳ），３７例６个月内ＣＤ４＋淋巴细胞降低至少２０％（ＣＤ４ｄｅｃｌｉｎｅ）。在１７２例对照和１８０例血清ＨＩＶ阳性受试者的比较中发现，其ＨＬＡ表型频率和单倍型频率没有显著差别，提示ＨＩＶ感染与ＨＬＡ无关联。然而，ＨＬＡ－Ｂ２１、ＨＬＡ－Ｂ８、ＨＬＡ－Ｂ３５表型及ＨＬＡ－Ａ１－Ｂ８、ＨＬＡ－Ｂ８－ＤＲ３、ＨＬＡ－Ａ１－Ｂ８－ＤＲ３单倍型与ＣＤ４阳性淋巴细胞下降，或与血清ＨＩＶ感染发展成ＡＩＤＳ病显著相关。１７例ＨＩＶ血清阴性高危人群中，无一携带单倍型ＨＬＡ－Ａ１－Ｂ８－ＤＲ３，提示该单倍型可能与ＨＩＶ感染的抗性相关。     

原发性高血压病遗传学研究

对５０例有家族史的遗性高血压患者进行家系、遗传度的调查及ＨＬＡ单倍型的关联分析，并以２１例无家族史的非遗传高血压及１００例正常无关人对照，结果发现：（１）遗传性高血压以多基因遗传为主，遗传度的加权平均值为５９．７２±８．１２％；（２）遗传性高血压与ＨＬＡ－Ｂ７５，ＤＲ１，ＤＱ７显著相关，Ｂ７５－ＤＱ７是连锁不平衡，非遗传传高血压ＨＬＡ－Ｂ８抗原偏高，提示原发性高血压具有遗传基础，ＨＬＡ基因可能存在     

HLA-Ⅱ型自动分类设备的开发

ＨＬＡ－Ⅱ型自动分类设备的开发［日］／田泽俊彦…／／ＢＭＥ．—１９９４，２（１２）．—６近年来，在发达国家中，为骨髓移植提供骨髓的人越来越多，对这些自愿者，主要是用ＬＣＴ（淋巴细胞抗毒实验）来对ＨＬＡ—　型进行分类，然而ＬＣＴ存在两个问题：①用ＬＣＴ...     

系统性红斑狼疮HLA－DPB_1和重组Ro（SS－A）／La（SS－B

系统性红斑狼疮ＨＬＡ－ＤＰＢ＿１和重组Ｒｏ（ＳＳ－Ａ）／Ｌａ（ＳＳ－Ｂ）蛋白抗体间无直接相关［英］／Ｙａｏｚ…／／Ｒｈｅｕｍａｆｏｌ．－１９９３，３．－１５５～１５８基因对系统性红斑狼疮（ＳＬＥ）血清学及临床表现异质性具有重要作用。已知ＨＬＡ－ＤＲ３...     

HLA－B51与中国北方汉族中的白塞氏病相关联

对１２０例白塞氏病患者和１００名无关健康人进行了ＨＬＡ－Ａ、－Ｂ、－Ｃ、－ＤＲ和－ＤＱ抗原分型检测，并使用Ｌｙｍｐｈｏ－Ｂ－Ｋｗｉｋ分离出Ｂ－淋巴细胞进行ＨＬＡ－ＤＱ和－ＤＲ分型，用琼脂糖电泳，免疫固定等技术测定了Ｂｆ和Ｃ４同种异型。其中，５５．８３％（６７／１２０）患者中检出ＨＬＡ－Ｂ５１，而对照组仅１２％。Ｘ２和ＲＲ分别为４５．５４和９．２７（Ｐ＜０．０００５）．完全型组ＨＬＡ－Ｂ５１更为常见（６２．７９％）；除患者组的Ｃ４ＡＱ０明显高于对照组外，其它的ＨＬＡ抗原、Ｂｆ和Ｃ４同种异型无明显的组间差异。结果提示：某些内在因素，诸如免疫遗传背景（存在有与ＨＬＡ－Ｂ５１密切相关的ＢＤ易感基因）在其病因及发病机理中可能起着重要作用。     

EB病毒感染对鼻咽上皮HLA表型改变的影响

用碱性磷酸酶抗碱性磷酸酶法（ＡＰＡＡＰ）检测ＨＬＡ－Ⅰ和ＨＬＡ－Ⅱ的表达。结果显示，体外培养的１０例人胚鼻咽上皮细胞被ＥＢ病毒感染后，ＨＬＡ－Ⅰ型抗原的表达无明显改变（阳性细胞为８５．８％±１７．１６％）；但ＨＬＡ－Ⅱ抗原的表达比对照组明显增高，两组阳性细胞各为５２．４％±１７．１６％和９．６７％±７．２３％，其差别有显著的统计学意义（Ｐ＜０．０５）。鼻咽活检组织中，１８例鼻咽癌细胞同时表达ＨＬＡ－Ⅰ和－Ⅱ两种抗原，并以后者为主（各为７２．２％和１００％），聚合酶链反应（ＰＣＲ）查到ＥＢ病毒ＤＮＡ的占９０％，与慢性鼻咽炎的差别有显著的统计学意义（Ｐ＜０．０５）。ＨＬＡ－Ⅱ表达增高可能在鼻咽癌的发生和发展中起着一定的作用。     

Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

The high prevalence of nasopharyngeal cancer (NPC) in Southern Asia and Mediterranean Northern Africa suggests genetic predisposition among other factors. While Human Leukocyte Antigen (HLA) haplotypes have been conclusively associated with NPC predisposition in Asians, Northern African Maghrebians have been less intensely studied. However, low resolution serological methods identified weak positive associations with HLA-B5, B13 and B18 and a negative with HLA-B14. Using sequence based typing (SBT), we performed a direct comparison of HLA class I frequencies in a cohort of 136 Tunisian patients with NPC matched for gender, age and geographical residence to 148 normal Tunisians. The bimodal age distribution of NPC in Maghrebians was also taken into account. HLA frequencies in normal Tunisians were also compared with those of Northern Moroccan Berbers (ME) to evaluate whether the Tunisian population in this study could be considered representative of other Maghrebian populations. HLA-B14 and -Cw08 were negatively associated with NPC (odd ratio = 0.09 and 0.18 respectively, Fisher p₂-value = 0.0001 and = 0.003). Moreover, positive associations were observed for HLA-B-18, -B51 (split of -B5) and -B57 (p₂-value < 0.025 in all) confirming previous findings in Maghrebs. The HLA-B14/Cw*08 haplotype frequency (HF) was 0.007 in NPC patients compared to 0.057 in both Tunisian (OR = 0.12; p₂-value = 0.001) and Moroccan controls. This study confirms several previous associations noted by serologic typing between HLA class I alleles and the prevalence of NPC in Maghrebians populations. In addition, we identified a putative haplotype rare in Tunisian patients with NPC that may serve as a genetic marker for further susceptibility studies.     

Familial exercise-induced anaphylaxis

We identified two siblings with exercise-induced anaphylaxis who share the HLA haplotype A3-B8-DR3 with their atopic father. The index case, a 16-year-old female, noted initial episodes at age 13. Intense pruritus, urticaria, facial edema, choking sensation, nausea, hypothermia, and collapse followed vigorous running but not swimming, cycling, racquetball, solar exposure, or cold exposure. Neither antihistamine, antiserotonin, anticholinergic nor epinephrine therapy was entirely effective or protective; only modification of running prevented episodes. Three similar episodes were noted at age 15 years by a brother who, now age 25, relates a 4-year history of seasonal rhinitis and exercise-related urticaria without anaphylactoid reaction. The remainder of the family (father, 47; mother, 46; brother, 22 years) does not have exercise intolerance. The father has allergic rhinitis; his nephew suffers exercise-induced urticaria without collapse. HLA typing revealed the father to be A1-B8-DR3, A3-B8-DR3; the symptomatic daughter to be A3-B8-DR3, A30-B5-DR8; and the symptomatic son to be A3-B8-DR3, A30-B5-DR8. The asymptomatic mother was A30-B5-DR8, A2-B7-DR5 and the asymptomatic son A1-B8-DR3, A30-B5-DR8. We describe exercise-induced anaphylaxis in a unique familial setting, perhaps linked to the HLA haplotype A3-B8-DR3.     

Human leukocyte antigen class I and MICA haplotypes in a multicase family with Cladophialophora carrionii chromoblastomycosis

Previous studies carried out in an endemic semiarid region northwest of Venezuela at Falcon State have shown a prevalence of 15.4/1000 of chromoblastomycosis following traumatisms with xenophile vegetation infected with Cladophialophora carrionii. We performed high-resolution DNA typing of human leukocyte antigen (HLA)-A, -B and -C and major histocompatibility complex class I chain related gene A (MICA) alleles and segregation analysis in 49 members of one extended family with 12 affected individuals, who have lived for approximately 70 years in this endemic zone. None of the alleles, haplotypes or genotypes is shared by all the patients. No deviation from the expected HLA haplotype distribution or association of chromoblastomycosis with HLA-A, -B and -C haplotypes was observed. Further, a haplotype-sharing transmission/disequilibria testing of 11 nuclear families did not give enough evidence to claim linkage (P = 0.398), suggesting that genes located in the short arm of chromosome 6 may not be relevant in the immune response toward infection with C. carrionii in this Venezuelan endemic zone. Deleted MICA alleles on HLA-B*4802 haplotypes were present among several members of the extended family, but only two of them were affected.     

HLA Haplotype A33-B58-Cw10 May Modulate Radiographic Development of Bamboo Spine in Taiwanese Patients with Primary Ankylosing Spondylitis

Objective: To evaluate the possible relationship between HLA alleles and bony ankylosis of the spine (bamboo spine) in Taiwanese patients with ankylosing spondylitis (AS).Methods: A small cohort of HLA-B27 positive AS patients was conducted to analyze the effects of alleles and haplotypes on the development of bamboo spine. DNA typing of HLA class I and class II genes were performed by SSP method on primary ankylosing spondylitis patients with bamboo spine (n = 84) and spinal enthesopathy controls (n = 228). Odds ratios with 95% confidence intervals and P value were estimated. Determination of the most probable HLA haplotypes on all patients were constructed by comparison of the alleles carried by each patient with the HLA haplotype database established in Taiwanese population studies using homozygosity approach [1] and by expectation-maximum algorithm [2].Results: Allele frequencies of HLA A33, B58, Cw10, DR4, DR17 and DQ2 were significantly lower in bamboo patients as compared to non-bamboo controls. In contrast, allele frequencies of A24, B54, Cw15, DR11 and DR14 were significantly higher in bamboo patients. Less remarkably, high frequencies of B39, B51, Cw1 and Cw2 alleles were also noted in bamboo patients. Considering linkage disequilibria of alleles in haplotypes, HLA-A11-B27-Cw12 was the most common haplotype in both bamboo and non-bamboo groups (95.23% vs. 91.22%, respectively, P = 0.238). Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 were significantly lower in bamboo patients as compared to those in controls (P < 0.001, P = 0.001, P = 0.002, respectively).Conclusion: Haplotypes A33-B58-Cw10, A33-B58-Cw10-DR13 and A33-B58-Cw10-DR17 showed a strong association with bamboo spine in Taiwanese AS patients. Detection of such haplotypes might be a great aid in the management of patients with the disease.     

HLA haplotypes and hayfever: a possible protective role

The HLA haplotype frequencies of European asthmatic children and their immediate families were studied, and a disassociation between haplotype A1-B8 and skin sensitivity to grass pollens was found, suggesting that within this allergic population, possession of the haplotype A1-B8 conferred possible protection against grass pollinosis. There was no association between A1-B8 and clinical asthma or between it and skin sensitivity to the house dust mite.     

造血干细胞移植56例人类白细胞抗原基因和单倍型分析

背景：收集56例欲行造血干细胞移植的供受者,均为无血缘关系的江西省汉族人群。了解个体的人类白细胞抗原基因型和单倍型。 目的：分析56例造血干细胞移植供受者的人类白细胞抗原基因频率,单倍型频率。 方法：收集56例欲行造血干细胞移植的供受者,均无血缘关系的江西省汉族人群。应用PCR-SSP的方法进行人类白细胞抗原(HLA)-A、B、DRB1基因分型,计算出HLA-A、B、DRB1各位点的基因频率和单倍型频率。 结果与结论：56例供受者测出HLA-A位点等位基因8种,HLA-B位点等位基因19种,HLA-DRB1位点等位基因13种,呈现出丰富的基因多态性。56例供受者两位点共224条等位基因中,A﹡02-B﹡46、A﹡11-B﹡40、B﹡46-DRB1﹡09单倍型的频率高于0.10。有10种A-B单倍型,4种B-DRB1单倍型呈现出显著的连锁不平衡。提示江西省汉族人群人类白细胞抗原基因具有较丰富的基因多态性。     

西北地区汉族人群HLA-A、-B、-DRB1基因座单倍型分析

目的 分析西北地区汉族群体HLA-A、-B和-DRB1基因座等位基因频率和HIA-A-B、B-DRB1和A-B-DRB1单倍型，获得单倍型频率数据。方法 采用序列特异性寡核苷酸探针反向斑点杂交技术对西北地区62个家系和101个无关个体HLA-A、-B和-DRB1基因座进行基因分型，分析HLA单倍型。结果 在西北地区汉族人群中检出15个HLA-A等位基因，28个HLA-B等位基因，13个HLA-DRB1等位基因，A02、A11、A24、B13、B15、1340、DRB1＊04、DRB1＊07、DRB1＊09和DRB1＊15基因频率较高（〉10％），A02（0．3244）、B13（0．1200）和DRB1＊15（0．1400）等位基因频率最高。分析得出HLA-A-B、B-DRB1、A-B-DRB1单倍型分别有122、147和278种，83种A-B-DRB1单倍型有至少两条以上相同的单倍型，占总单倍型数的18．44％（83／450）。A30-B13-DRB1＊07、A02-B46-DRB1＊09、A01-B37-DRB1＊10、A24-B15-DRB＊15、A02-B46-DRB1＊08、A33-B58-DRB1＊03是最常见的单倍型。结论 西北地区汉族群体HLA单倍型多态性较为丰富，等位基因频率和单倍型频率数据可用于骨髓移植供者的选择、法医学亲权鉴定以及人类学研究。     

HLA polymorphism and probability of finding HLA-matched unrelated marrow donors for Chinese in Taiwan

Tzu Chi Taiwan Marrow Donor Registry (TCTMDR) was established in 1993 to recruit and HLA-type volunteers who would be willing to donate bone marrow. TCTMDR is currently the largest marrow registry for Chinese in the world, with over 150,000 prospective donors registered as of July 1997. We present here the gene and haplotype frequencies based on 80,353 HLA class I-typed and 18,217 HLA class II-typed healthy Chinese in Taiwan. The resulting frequencies are used for estimating the probability of finding an HLA-matched donor for a patient. The common HLA class I antigens include Al (gene frequency: 32.9%), A2 (29.7%), A24 (17.5%) and A33 (11.0%); B60 (18.1%), B46 (12.8%), B58 (9.8%) and B13 (7.8%); Cw3 (51.4%), Cwl (11.6%) and Cw7 (8.6%). The common HLA class II antigens are DR4 (16.6%), DR9 (15.6%), and DR12 (14.0%); DQ7 (20.7%), DQ9 (12.7%), and DQ5 (12.1%). The common two-locus haplotypes observed with a P -value less than 0.001 are A2-B46 (haplotype frequency: 8.5%), A33-B58 (7.5%), A11-B60 (6.6%); B58-DR17 (7.0%), B46-DR9 (6.4%) and B60-DR4 (4.9%). The common three-locus haplotypes are A33-B58-DR17 (5.3%), A2-B46-DR9 (3.9%) and A11-B60-DR4 (2.0%). As expected, the gene frequency pattern of Taiwanese is more closely related to that of southern Hans than to the pattern of northern Hans, Japanese, Caucasians and African-Americans. Using our registry, 323 of 571 domestic patients (57%) successfully identified one or more matched donors. The empirical result correlated well with a mathematical simulation having an estimated 59% match when donor pool reaches 150,000.     

HLA-A, -B, -DR haplotype frequencies from DNA typing data of 26,266 Chinese bone marrow donors

HLA phenotypes of 26,266 Chinese individuals who were recruited as potential hematopoietic stem cell donors by the Shanghai Red Cross Marrow Donor Registry, part of the China Marrow Donor Program, were determined for HLA-A, -B, and -DRB1 alleles at low to intermediate resolution using DNA-based typing methods. The large sample size of the study allowed accurate calculation of the Chinese HLA haplotype frequencies. The observed alleles correspond to 19 HLA-A, 44 -B, and 13 -DR split antigens. The serologic equivalents of HLA-A36, -A80, -B78, and -DR18 alleles were not observed. A total of 2,241 distinct HLA-A, -B, -DRB1 haplotypes were identified. Three-locus haplotype frequency was estimated using the maximum likelihood method. The lowest haplotype frequency that can be reliably estimated at a 95% confidence level was 0.000057. Using this cutoff value, 1,220 haplotypes (54%) were statistically reliable and their cumulative haplotype frequency was 0.9730. The cumulative haplotype frequency of the remaining 1,021 haplotypes (46%) was 0.0270. A regression equation of p = 0.192 log N - 0.576 was derived to estimate the probability (p) of finding an HLA-A, -B, -DR split antigens-matched donor in a pool of N Chinese donors.     

HLA Haplotypes In 250 Families: The Baylor Laboratory Results And A Perspective On A Core NGS Testing Model For The 17th International HLA And Immunogenetics Workshop

Since their inception, the International HLA & Immunogenetics Workshops (IHIW) served as a collaborative platform for exchange of specimens, reference materials, experiences and best practices. In this report we present a subset of the results of human leukocyte antigen (HLA) haplotypes in families tested by next generation sequencing (NGS) under the 17th IHIW. We characterized 961 haplotypes in 921 subjects belonging to 250 families from 8 countries (Argentina, Austria, Egypt, Jamaica, Germany, Greece, Kuwait, and Switzerland). These samples were tested in a single core laboratory in a high throughput fashion using 6 different reagents/software platforms. Families tested included patients evaluated clinically as transplant recipients (kidney and hematopoietic cell transplant) and their respective family members. We identified 486 HLA alleles at the following loci HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, -DPB1 (77, 115, 68, 69, 10, 6, 4, 44, 31, 20 and 42 alleles, respectively). We also identified nine novel alleles with polymorphisms in coding regions. This approach of testing samples from multiple laboratories across the world in different stages of technology implementation in a single core laboratory may be useful for future international workshops. Although data presented may not be reflective of allele and haplotype frequencies in the countries to which the families belong, they represent an extensive collection of 3rd and 4th field resolution level 11-locus haplotype associations of 486 alleles identified in families from 8 countries.