超声超微细彩色血管成像技术评价经肝动脉化疗栓塞治疗的原发性肝癌患者肿瘤血供效能初步应用研究

目的 探讨应用超声超微细彩色血管成像（SMI）技术评价经导管肝动脉化疗栓塞术（TACE）治疗的原发性肝癌（PLC）患者病灶血供情况。方法 2014年1月~2015年12月在我院接受TACE治疗的PLC患者45例（56个病灶）,术后1个月,接受增强CT、超微细彩色血流成像（SMI）和彩色多普勒血流成像（CDFI）检查。以增强CT作为对照,绘制受试者工作特征曲线（ROC曲线）,并计算曲线下面积（AUC）,比较同一病灶的血供情况。结果 增强CT评估病灶血供的能力优于CDFI（x²=38.205,P<0.001）或SMI（x²=12.010,P=0.001）;以增强CT为标准,SMI评估病灶血供的能力优于CDFI（x²=9.583,P=0.002）;进一步对不同方法诊断病灶血供的效能显示,SMI检查的ROC曲线下面积大于CDFI（P=0.031）,SMI判断病灶血供的灵敏度、准确度和阴性预测值分别为62.4%、58.9%和31.5%,均优于CDFI的30.4%、28.4%和21.1%（x²=20.612,P<0.001;x²=10.251,P=0.001;x²=2.956,P=0.041）;SMI可以清晰地显示直径<2.0 cm的病灶内部血流,但是CDFI未显示血流信号,SMI评估病灶血供的能力优于CDFI（x²=5.758,P=0.016）;对于直径≥2 cm的病灶,SMI和CDFI均可显示病灶血流,但是SMI评估病灶血供的能力优于CDFI（x²=6.560,P=0.010）。结论 SMI技术是一种新型血流成像技术,能较好地检测病灶的血供情况,为临床评价PLC患者在TACE术后疗效提供了一种新的方法。     

肝癌组织IFITM3蛋白表达水平及其与肝细胞癌患者手术切除术后肝内肿瘤复发的相关性分析*

目的 探讨肝细胞癌（HCC）组织干扰素诱导跨膜蛋白 3（IFITM3）表达水平及其临床意义。方法 在我院接受根治性手术切除治疗的43例HCC患者,术中取癌组织和癌旁肝组织,分别采用Western blot法和免疫组化法检测组织IFITM3蛋白表达情况,比较肝内肿瘤复发与未复发患者癌组织IFITM3表达的差异。结果 经Western blot法检测肝癌组织IFITM3表达水平为（1.2386±0.1901）,显著高于癌旁组织的（0.9496±0.0995,t=8.832,P=0.000）;免疫组化法检测显示肝癌组织IFITM3蛋白阳性率为72.1%（31/43）,明显高于癌旁组织的14.0%（6/43,x²=29.647,P=0.000）;中分化肝癌组织IFITM3蛋白阳性率为90.9%（10/11）,低分化肝癌组织为95.2%（20/21）,均明显高于高分化组的9.1%（1/11）（x²=14.727, P=0.000;x²=23.748,P=0.000）;术后复发组癌组织IFITM3蛋白阳性率为81.0%（17/21）,未复发组为22.7%（5/22）,两者比较差异具有统计学意义（x²=14.578,P=0.000）。结论 HCC组织IFITM3蛋白呈高表达,且肝癌分化越差,IFITM3表达也越强,并可能与术后肿瘤复发有关。     

广州地区424例乙型肝炎患者病毒基因亚型分布与乙型肝炎疾病谱的关系探讨*

目的调查广州地区乙型肝炎病毒（HBV）基因亚型分布情况, 并探讨其与HBV感染疾病谱的关系。方法采用直接测序法测定S基因序列并构建基于S基因进化树,对424例HBV感染者进行研究,随机选择慢性乙型肝炎（CHB）137例,HBV相关慢加急性肝衰竭（HB-ACLF）90例,肝硬化（LC）90例和肝细胞癌（HCC）107例,应用SPSS 13.0软件进行x²检验、方差分析和多元Logistic回归分析。结果在424例HBV感染者中,B2亚型 269例（63.44%）,C1亚型117例（27.59%）,C2亚型36例（8.49%）,C5亚型 2例（0.47%）,未发现其他亚型;CHB患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为70.1%、24.09%、5.11%和0.73%;HB-ACLF患者感染HBV B2亚型、C1亚型和C2亚型分别为87.78%、7.78%、4.44%,其中HBV B2基因亚型显著高于CHB（x²=9.641,P=0.002）、LC（x²=19.565,P=0.000）、HCC患者（x²=26.789,P=0.000）;LC患者感染HBV B2亚型、C1亚型和C2亚型分别为50.00%、36.67%、13.33%,其中HBV C1和C2亚型显著高于CHB患者（x²=6.262,P=0.012;x²=4.790,P=0.029）或HB-ACLF患者（x²=25.894,P=0.000;x²=4.390,P=0.036）;HCC患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为45.79%、41.12%、12.15%、0.93%,其中HBV C1和C2亚型也显著高于CHB患者（x²=11.264,P=0.001;x²=3.957,P=0.047）或HB-ACLF患者（x²=28.327,P=0.000;x²=3.904,P=0.048）;LC和HCC患者HBV C1和C2基因亚型无明显差异（x²=0.429,P=0.512;x²=0.804,P=0.833）;多因素Logistic回归分析提示B2亚型是HB-ACLF发生的危险因素（OR=2.597,95%CI=1.145~5.891,P=0.022）,C型是HCC发生的危险因素（OR=3.257,95%CI=1.49~7.194,P=0.003）。结论广州地区HBV基因亚型主要由B2、C1和C2亚型构成,同时也存在C5亚型;广州地区B2亚型感染者可能更易发生HBV相关慢加急性肝衰竭,而C1和C2亚型感染者可能更易进展为肝硬化和肝细胞癌。     

汉族人群乙型肝炎病毒感染者外周血IL-28B基因多态性研究*

目的 分析乙型肝炎病毒（HBV）感染者外周血IL-28B基因型和等位基因频率分布,并探讨其与疾病病程和进展的关系。方法 本研究纳入江苏籍汉族健康人群145例和453例HBV感染者,后者包括无症状HBV携带者（ASC）45例,慢性乙型肝炎患者（CHB）181例,肝硬化（LC）患者69例,肝细胞癌（HCC）患者79例,乙型肝炎肝衰竭（LF）患者79例,采用PCR法和直接测序法检测外周血IL-28B基因rs12979860和rs8099917多态性位点。采用Pearson x²检验对IL-28B rs8099917与rs12979860位点进行Hardy-Weinberg平衡检验,计量资料以（x±s）表示,计数资料采用例数表示。应用SPSS 17.0软件进行方差分析、x²检验和Binary Logistic回归分析。结果 IL-28B基因rs12979860位点有CC、CT和TT 3个基因型,LF患者CC型和C等位基因频率分别为96.2%和98.1%,显著高于健康人群的87.6%和93.1%（OR=0.257,95%CI=0.068~0.973,P=0.045;OR=0.255,95%CI=0.070~0.928,P=0.038）;IL-28B基因rs8099917位点有TT 、TG和GG 3个基因型,LC患者TT型和T等位基因频率分别为92.8%和96.4%,显著高于健康人群的86.2%和92.4%（OR=0.288,95%CI=0.087~0.948,P=0.041;OR=0.299,95%CI=0.096~0.926,P=0.036）。结论 江苏地区汉族人群IL-28B基因多态性与HBV感染后不同疾病表型相关,IL-28B基因rs12979860的C等位基因和IL-28B基因rs8099917的T等位基因可能是HBV感染后病情进展的影响因素。     

血HLA-A、-B、-C、-DRB1、-DQB1等位基因多态性与肝细胞癌发生关联研究

目的探讨中国广东汉族人血HLA-A、-B、-C、-DRB1、-DQB1等位基因与HBV感染罹患肝细胞癌(HCC)的关联性。方法采用聚合酶链反应-直接测序分型法检测广东地区56例HCC患者和97例健康志愿者血HLA-A、-B、-C、-DRB1、-DQB1基因型。结果 HCC患者血HLA-A*02:03和A*02:07等位基因频率明显高于健康人(0.116071对0.046392和0.178571对0.061856,χ~2=5.167、χ~2=10.33,P=0.023、P=0.001);HCC患者血HLA-B*46:01等位基因频率为0.205357,明显高于健康人的0.108247(χ~2=5.439,P=0.02);HCC患者血HLA-DRB1*14:54和DRB1*12:02等位基因频率明显高于健康人(0.089286对0和0.142857对0.06701,χ~2=14.502、χ~2=4.761,P=0.000、P=0.026);HCC患者血HLA-DQB1*05:03等位基因频率为0.098214,明显高于健康人的0.036082(χ~2=4.951,P=0.026);HCC患者血HLA-A*30:01等位基因频率为0.017857,明显低于健康人的0.082474(χ~2=5.355,P=0.021);HCC患者血HLA-B*13:02等位基因频率为0.008929,明显低于健康人的0.07732(χ~2=6.702,P=0.01)。结论在中国广东地区人群中,HLA-A*02:03、A*02:07、HLA-B*46:01、HLA-DRB1*14:54、DRB1*12:02、HLA-DQB1*05:03与感染HBV的HCC发病有关,而与HLA-A*30:01和HLA-B*13:02可能无关。     

超声引导下经皮射频消融治疗小肝癌患者疗效及预后分析*

目的 比较超声引导下经皮射频消融与肝切除术治疗小肝癌患者的疗效及分析影响生存的危险因素。方法 2011年1月~2015年4月在我院接受治疗的107例肝细胞癌（HCC）患者,接受超声引导下射频消融治疗58例,接受肝叶切除术治疗49例。术后随访3年,采用Cox单因素和多因素回归分析影响HCC患者生存的独立危险因素。结果 治疗后,射频消融患者血清ALT水平显著低于肝切除术组（P<0.05）,而血清ALB水平显著高于肝切除术组（P<0.05）;两组术后并发症发生率（10.3%对16.3%）比较,差异无统计学意义（P>0.05）;射频消融治疗患者1 a、2 a和3 a总生存率分别为84.5%（49/58）、65.5%（38/58）和44.8%（26/58）,而肝切除术组则分别为85.7%（42/49）、67.3%（33/49）和46.9%（23/49）,差异不具有统计学意义（x²=0.032,P=0.859;x²=0.040,P=0.842;x²=0.048,P=0.827）; Cox单因素分析结果显示肿瘤数目（HR=0.372,95%CI:0.105~0.876,P=0.033）与HCC患者无瘤生存时间有关,而血清AFP水平（HR=3.043,95%CI:1.007~5.248,P=0.035）、肿瘤数目（HR=0.871,95%CI:0.344~0.902,P=0.401）和肿瘤直径（HR=1.631,95%CI:1.273~3.045,P=0.005）与HCC患者总生存时间有关;Cox多因素回归分析结果显示肿瘤数目多（HR=0.087,95%CI:0.045~0.498,P=0.009）是影响HCC患者无瘤生存的独立危险因素,而肿瘤分化低（HR=2.974,95%CI:1.865~4.097,P=0.046）、肿瘤数目多（HR=0.062,95%CI:0.033~0.378,P=0.002）和肿瘤直径大（HR=2.216,95%CI:1.778~5.026,P=0.007）是影响HCC患者总生存时间的独立危险因素。结论 超声引导下经皮射频消融治疗与肝切除术治疗小肝癌患者的临床疗效相当,但射频消融治疗创伤小,术后恢复快,对肝功能的影响小。     

乙型肝炎肝硬化患者院内获得性感染相关危险因素分析*

目的 分析影响乙型肝炎肝硬化患者发生院内获得性感染相关的危险因素,以为临床诊治提供可借鉴的经验。方法 2015年1月~2017年1月在我院诊治的乙型肝炎肝硬化患者280例,查阅出院病历,结合临床症状、体征、血白细胞或/和中性粒细胞比率增高、血降钙素原水平升高、细菌培养阳性和影像学检查结果并参照卫生部2001年颁布的《医院感染诊断标准》诊断感染,对影响患者院内感染的因素先行单因素分析,再对有显著意义的因素采用多元Logistic回归分析。结果 在280例乙型肝炎肝硬化患者中,发生院内感染57例（20.4%）,其中自发性细菌性腹膜炎18例（31.6%）,呼吸道感染12例（21.1%）,胃肠道感染10例（17.5%）,泌尿系感染7例（12.3%）和败血症10例（17.5%）;经单因素分析显示,年龄（x²=7.416,P=0.006）、住院时间（t=28.247,P<0.001）、血清白蛋白（t=2.661,P=0.008）、CD4⁺T淋巴细胞ATP值（t=8.122,P<0.001）、Child-Pugh分级（x²=10.577,P=0.005）、侵入性操作（x²=29.214,P<0.001）、腹水（x²=25.776,P<0.001）、消化道出血（x²=111.434,P<0.001）为影响乙型肝炎肝硬化患者发生院内获得性感染的相关危险因素,而感染与患者性别和是否发生肝性脑病无显著性相关（P>0.05）;经多因素Logistic回归分析,结果显示,年龄、侵入性操作、腹水、消化道出血、住院时间和血清白蛋白水平是发生院内获得性感染的独立危险因素。结论 乙型肝炎肝硬化患者易发生院内感染,尤其是年龄较大、肝储备功能差、出现并发症和住院时间较长者。临床医生应该对这类患者给予特殊的关怀,严格无菌操作,预防并发症发生,促进肝功能恢复。     

ERCP引导下射频消融联合化疗治疗胆管癌患者疗效及影响预后因素分析

目的 探讨在内镜逆行性胰胆管造影术（ERCP）引导下射频消融结合化疗治疗胆管癌患者的疗效及影响预后的因素。方法 2009年1月~2014年12月我院收治的96胆管癌患者被分为对照组48例和观察组48例,给予对照组患者经ERCP引导下行射频消融治疗,观察组在对照组治疗的基础上予以联合化疗治疗,比较两组近期临床疗效,统计分析所有患者的预后生存情况,采用Cox回归分析影响患者术后生存的相关因素。结果 治疗后,观察组患者血清TBIL为（72.6±22.2） μmol/L,GGT为（262.2±64.6） U/L和ALP为（206.4±62.6） U/L,均明显低于对照组的（102.6±32.4） μmol/L、GGT（382.4±102.4） U/L和ALP（284.4±86.4） U/L,而ALB（42.4±10.8）g/L明显高于对照组[（36.2±10.6） g/L,P<0.05];观察组患者近期临床总有效率（91.6%）明显高于对照组（75.0%,x²=4.800,P=0.028）;观察组和对照组3 a生存率分别为58.3%和29.2%（x²=8.296,P=0.004）,两组3 a无复发生存率分别为54.1%和25.0%（x²=8.537,P=0.003）;单因素Cox回归分析发现,年龄、肿瘤位置、数目、分化程度、临床分期、CEA水平和治疗方法均可能影响胆管癌患者的预后（P<0.05）;多因素Cox回归模型分析发现,肿瘤低分化（HR=1.84,95%CI:1.05~3.23）、Ⅲ、Ⅳ期（HR=1.76,95%CI:1.03~3.02）、发生转移（HR=1.81,95%CI:1.05~3.12）和术后未进行化疗（HR=1.84,95%CI: 1.03~3.27）为影响胆管癌患者预后的独立危险因素（P<0.05）。结论 ERCP引导下射频消融结合化疗可明显提高胆管癌患者近期临床治疗有效率、延长生存时间和改善预后。针对影响胆管癌患者预后的独立危险因素进行及时处理,或许能提高疗效。     

冷循环微波消融联合肝动脉灌注化疗栓塞治疗原发性肝癌患者疗效及安全性研究

目的 探讨冷循环微波消融联合肝动脉灌注化疗栓塞（TACE）治疗原发性肝癌患者的疗效和安全性。方法 将72例原发性肝癌患者随机分成观察组和对照组,每组36例。给予观察组冷循环微波消融联合TACE治疗,对照组行单纯TACE治疗,比较总有效率、生存率、血清甲胎蛋白（AFP）变化和不良反应。结果 在治疗后6个月,观察组总有效率（88.9%）显著高于对照组（69.4%,x²=4.12,P=0.04）;观察组2 a生存率（66.7%）显著高于对照组（41.7%,x²=4.5,P=0.03）;观察组血清AFP下降率（83.3%）显著高于对照组（61.1%,P<0.05）;所有患者均未出现严重的不良反应。结论 冷循环微波消融联合TACE治疗原发性肝癌患者安全有效。     

肝细胞癌患者IL-18基因-137G/C和-607A/C位点单核苷酸多态性变化及其意义探讨*

目的 探讨肝细胞癌（HCC）患者白细胞介素-18（IL-18）基因-137G/C和-607A/C位点单核苷酸多态性（SNP）的变化。方法 在178例伴有HBV感染的HCC患者和251例健康人,取外周静脉血提取DNA,采用聚合酶链反应-连接酶检测反应（PCR-LDR）行基因分型,测定IL-18基因-137G/C和-607A/C位点SNP。结果 HCC患者和健康人IL-18-37 G/C基因GG基因型、GC基因型和CC基因型分布频率分别为75.3%对47.0%（P<0.05）、20.8%对51.4%（P<0.05）和3.9%对1.6%（P>0.05）,G等位基因和C等位基因分布频率分别为93.6%对72.7%（P<0.05）和6.4%对27.3%（P<0.05）;HCC患者和健康人IL-18-607A/C位点AA基因型、AC基因型和CC基因型分布频率分别为37.6%对13.5%（P<0.05）、43.3 %对66.9%（P<0.05）和19.1%对19.5%（P>0.05）,A等位基因和C等位基因分布频率分别59.3%对47.0%（P<0.05）和40.7%对53.0%（P<0.05）;HCC组IL-18-137G/C位点的GG基因和G等位基因频率显著高于健康人（P<0.05）,HCC组IL-18-607A/C位点的AA基因和A等位基因频率也显著高于健康人（P<0.05）,提示携带IL-18-137G/C和IL-18-607A/C位点基因型和A等位基因者罹患HCC的风险增加。结论 携带IL-18基因-137G/C位点GG基因型和G等位基因以及-607A/C位点AA基因型和A等位基因者可能更容易发生HCC,对HBV感染者筛查这些基因可能有助于早期发现肝肿瘤,以利于早期处理和改善预后。     

HLA Class I and Class II Genes Distribution of the Sistanis in Iran

Background: The high polymorphism in the human leukocyte antigen (HLA) genes can be used as an identity of individuals to compare with other populations. This extreme polymorphism in the HLA system is accountable for the differences in alleles and haplotypes among ethnic groups, populations, and the inhabitants of many regions. Objective: To define the frequency of HLA alleles and haplotypes among the Sistanis, Sistani/Zaboli population in Iran. Methods: In this study, genotyping of class I (A, B, C) and class II HLA (DRB1, DQA1, DQB1) loci were determined in 90 unrelated Iraninan Sistani people and the results were compared with 474,892 HLA chromosomes from a diverse worldwide population. Results: The highest frequently observed alleles in this study were A*02:01, B*35:01, C*12:03, C*06:02, DRB1*11, DQA1*05:05, and DQB1*03:01. Furthermore, the most frequent 3-locus haplotypes were A*02:01-B*50:01*C*06:02, DRB1*11-DQB1*03:01-DQA1*05:05, and A*02:01-B*50:01-DRB1*07. The most occurring 4-locus haplotypes were A*02:01-B*50:01-C*06:02-DRB1*07 and A*02:01-B*50:01-DRB1*07-DQB1*02:01. A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01 and A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01-DQA1*02:01 were determined to be the predominant 5- and 6-locus haplotypes, respectively. The heat maps and multiple correspondence analyses based on the frequency of HLA alleles showed that Sistanis share a common genetic inheritance with other Iranian ethnic groups such as the people from Yazd and Fars except some differences with Baluchis, Iranian Jews, Lurs of Kohgiluyeh/Buyerahmad, and Arabs of Fars, which may arise from the admixture of these groups or with foreign subgroups over centuries, and also a close relatedness with some European populations. Conclusion: These data could be useful for finding better donor matches for organ transplantation among Sistanis or other related Iranian ethnic groups, epidemiological studies of HLA-associated diseases, handling HLA genomics and mapping the migration pattern of different ethnic group.     

Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source

The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included chi(2) testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < or = .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with only 37% of those with chronic infection (P <.0001). The haplotypes A*03-B*07-DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501 are associated with viral clearance (P =.004 and.01, respectively). By multiple logistic regression analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99). The haplotype A*01-B*08-Cw*07-DRB1*03011-DQB1*0201 is associated with chronic infection (P =.002), being independent for DQB1*0201 (OR 0.27). In conclusion, certain class I alleles are associated with outcome in this homogeneous cohort. More significantly, either HLA-A*03, -DRB1*0101, or -*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV.     

Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela.

AIMS: Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations. METHODS: To analyse the molecular basis of these associations in Venezuela (mestizo population), we examined the frequency of human leucocyte antigens (HLA)-A -B -C, HLA-DQ and HLA-DR genes by low- and high-resolution oligonucleotide typing in a population of 41 type 1 AIH patients and 111 ethnic- and aged-matched healthy subjects. RESULTS: The frequencies of both DRB1(*)1301 (P<0.0001) and DRB1*0301 (P<0.005) were significantly higher in patients than in controls. In addition, patients showed a strong association with the DRB3 allele (P<0.01). In contrast, the DQB1*04 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A*01-B*08-DQB1*02-DRB1*03-DRB3, DQB1*05-DRB1*1301, DQB1*06-DRB1*1301 and A*02-DRB1*1301, B*45-DRB3 were significantly increased in type 1 AIH patients compared with the controls (P<0.01). CONCLUSIONS: In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles. In addition, our findings suggest that protection against disease might be conferred by the DQB1*04 allele, with distinct ethnic differences from other populations.     

Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine

To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12-B*38 haplotype was associated with higher cellular immune responses to measles (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype was associated with high levels of IgG antibody to measles virus (P=.09) but low levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative responses to both measles (P=.01) and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels (P=.02) and higher rubella virus-specific lymphoproliferation (P=.002). Better characterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.     

广西梧州籍汉族α-地中海贫血患者HLA-A、B等位基因多态性及单倍型分析

目的分析广西梧州籍汉族α-地中海贫血患者人类白细胞抗原（HLA）-A、B在高分辨基因分型水平上的等位基因多态性和单倍型的分布特征。方法采用聚合酶链反应-直接测序分型法（PCR-SBT）,对广西梧州籍汉族117例α-地中海贫血患者的HLA-A、B位点进行高分辨基因分型,用直接计数法计算等位基因频率,应用Arlequin V3.5软件,以最大似然法分析单倍型频率。结果在117例α-地中海贫血患者中共检出高分辨HLA-A等位基因17个,HLA-B等位基因33个。A位点等位基因频率最高的是A＊11：01（27.35%）,B位点等位基因频率最高的是B＊40：01（15.38%）和B＊46：01（14.96%）。频率最高的HLA-A-B单倍型有A＊33：03-B＊58：01（11.49%）、A＊02：07-B＊46：01（8.33%）、A＊11：01-B＊40：01（6.34%）。连锁不平衡最显著的单倍型是A＊33：03-B＊58：01、A＊02：07-B＊46：01、A＊74：02-B＊51：01、A＊02：03-B＊38：02、A＊11：02-B＊27：04。结论广西梧州籍汉族α-地中海贫血患者HLA-A、B等位基因具有较高的多态性,其双座位单倍型具有地区性遗传特征。     

Frequency of DRB1-DQB1 two-locus haplotypes in tuberculosis: preliminary report

Analysis of correlation between tuberculosis (TB) and human leukocyte antigen (HLA) in populations from Asia and Latin America has shown conflicting results. The aim of this study was to evaluate the frequency of HLA-DRB1-DQB1 two-locus haplotypes of 61 TB patients and 125 healthy volunteers in the same ethnic group in Poland. DRB1 and DQB1 alleles were determined by PCR-SSP "low-resolution" and "high-resolution" methods. Our study showed that DRB1*1601 and DQB1*0502 alleles were more frequent, whereas DQB1*0201 was rarer in TB than in controls. DRB1*16-DQB1*05, DRB1*04-DQB1*03 and DRB1*1601-DQB1*0502 haplotype were more common, and DRB1*11-DQB1*03 less frequent in TB in comparison to controls. Positive linkage disequilibrium (LD) for DRB1*01-DQB1*05, DRB1*03-DQB1*02, DRB1*11-DQB1*03, DRB1*13-DQB1*06 and DRB1*15-DQB1*06 was found in controls. A trend towards the positive LD for DRB1*01-DQB1*05, DRB1*03-DQB1*02, DRB1*11-DQB1*03, DRB1*15-DQB1*06 and DRB1*16-DQB1*05 was shown in TB. The trend towards the positive LD for DRB1*16-DQB1*05 haplotype in TB patients was not observed in the control group. It seems likely that the presence of DRB1*1601, DQB1*0502 alleles and DRB1*1601-DQB1*0502, DRB1*04-DQB1*03, DRB1*14-DQB1*05 haplotypes may be related to a higher risk of developing TB, whereas low frequency of DQB1*0201 and DRB1*11-DQB1*03 haplotype may be linked to the resistance to TB.     

HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population

BACKGROUND & AIMS: Autoimmune pancreatitis is a distinctive disease entity characterized by high serum immunoglobulin G4 concentrations. Because of the close association between some autoimmune diseases and particular alleles of major histocompatibility complex genes, we investigated the association between HLA alleles and autoimmune pancreatitis. METHODS: HLA-A, -B, -C, -DR, and -DQ gene typing and HLA-DRB1, -DQB1, and -DPB1 allele typing were performed by the polymerase chain reaction sequence-specific primers method and the restriction fragment length polymorphism method, respectively, in 40 patients with autoimmune pancreatitis, 43 patients with chronic calcifying pancreatitis, and 201 healthy subjects. RESULTS: In patients with autoimmune pancreatitis compared with healthy subjects, we found a significant increase in DR4 (73% vs. 44%, corrected P = 0.01) and DRB1*0405 (58% vs. 21%, corrected P = 0.000026) and DQ4 (58% vs. 26%, corrected P = 0.001) and DQB1*0401 (58% vs. 21%, corrected P = 0.000017). The DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant association with any HLA class I antigens, in contrast to the B54-DRB1*0405-DQB1*0401 haplotype reported in autoimmune hepatitis. The frequencies of DRB1*0405 and DQB1*0401 were significantly high in patients with autoimmune pancreatitis compared with chronic calcifying pancreatitis. CONCLUSIONS: It is probable that DRB1*0405-DQB1*0401 haplotype is associated with autoimmune pancreatitis in the Japanese population.     

The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A,HLA-B,and HLA-DR matched unrelated donors

To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases. Thus, the role of the HLA class I allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival.     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients.METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai.Among CHB patients, 35 were treated with IFNα-1b for 24 wk.RESULTS: The frequencies of HLA-DRB1*06, DRB1*08and DRB1*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR = 3.837, P= 0.018;11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively); whereas that of DRB1*07 allele was lower (2.78% vs 7.75%,OR = 0.340, P = 0.046). The frequency of HLA-DRB1* 14allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs2.08%, OR = 10.444,P = 0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR = 0.167, P= 0.021).CONCLUSION: The polymorphism of HLA class Ⅱ may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1*06, DRB1*08, and DRB1*16 may be associated with chronicity of HBV infection, HLA-DRB1*07 with protection against HBV infection, and HLA-DRB1*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment.Compared with other HLA-DQB1 alleles, HLA-DQB1*07 may be associated with low response rate to IFN.     

HLA association of amoxicillin-clavulanate--induced hepatitis.

BACKGROUND & AIMS: Drug-induced immunoallergic hepatitis typically affects a minority of patients exposed to a particular drug. Its rarity is believed to be due to metabolic or immunologic idiosyncrasy. The presence of an immunologic idiosyncrasy might imply an HLA association. Previous studies reporting an HLA association of drug-induced hepatitis included only small numbers of patients and used serological HLA typing. METHODS: We studied 35 patients with biopsy-documented amoxicillin-clavulanate-induced hepatitis. HLA-A and -B were typed using alloantisera and compared with those of 300 controls (volunteer bone marrow donors). HLA-DRB and -DWB were typed by polymerase chain reaction-line probe assay, with 60 volunteer bone marrow donors serving as controls. RESULTS: The study group was characterized by a higher frequency of DRB1*1501-DRB5*0101-DQB1*0602 haplotype (57.1% vs. 11.7% in controls, P < 0.000005; after correction for the large number of comparisons, P < 0.0002). Patients with DRB1*1501-DRB5*0101-DQB1*0602 haplotype were more likely than patients without it to have a cholestatic (70% vs. 60%) or mixed (30% vs. 13%) than a hepatocellular pattern of hepatitis (0% vs. 27%) (P < 0.05). CONCLUSIONS: Amoxicillin-clavulanate-induced hepatitis is associated with the DRB1*1501-DRB5*0101-DQB1*0602 haplotype. The data support the view that an immunologic idiosyncrasy, mediated through HLA class II antigens, plays a role in the pathogenesis of drug-induced immunoallergic hepatitis. HLA association has a limited impact on the expression of hepatitis.