中国汉族强直性脊柱炎患者人类白细胞抗原-B27多态性研究

目的 本研究拟利用最新的人类白细胞抗原(HLA)-B27亚型数据,调查中国汉族强直性脊柱炎(AS)患者HLA-B27及其亚型的分布情况.方法 从我院脊柱关节炎患者数据库中随机抽取100例AS患者.用luminex液态芯片,结合聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)技术对HLA-B位点作低分辨分型.HLA-B27阳性者进一步用聚合酶链反应-序列特异性引物(PCR-SSP)法做高分辨HLA-B27亚型检测.结果 经随机抽样纳入无关AS患者98例,其中HLA-B27阳性93例,阳性率94.9%,其中B*2704亚型76例(81.7%),B*2705亚型12例(12.9%),B*2715亚型5例(5.4%).与另外2篇文献报道的HLA-B27阳性汉族健康人群比较,没有一致的证据表明HLA-B27亚型分布在AS患者和健康人群中存在差异.但这2项汉族健康人群中的研究均未发现B*2715亚型.结论 中国汉族AS患者B27亚型以B*2704为主,其次是B*2705.B*2715作为一个频率极低的等位基因,本组病例中发现5例,提示B*2715与AS发病存在关联.     

别嘌呤醇引起发疹型药疹8例及相关基因HLA-B* 5801检测

目的通过检测8例别嘌呤醇引起的发疹型药疹患者的HLA-B*5801等位基因,探讨别嘌呤醇引起的发疹型药疹与HLA-B*5801等位基因的相关性。方法收集本院2012年3月至2015年5月因别嘌呤醇所致的发疹型药疹患者8例,服用别嘌呤醇未发生药疹痛风患者30例,健康体检者120名。采集患者外周静脉血,提取DNA,利用PCR技术检测受试者HLA-B*5801基因型。结果 8例别嘌呤醇引起发疹型药疹患者中,3例患者HLA-B*5801等位基因阳性,阳性率为37.5%;30例服用别嘌呤醇未发生药疹的痛风患者中,2例患者HLA-B*5801等位基因阳性,阳性率为6.7%;120名健康受试者中,13名HLA-B*5801等位基因阳性,阳性率为10.8%。各组间比较差异无统计学意义(χ2=4.931,P0.05)。药疹组与非药疹组HLA-B*5801基因阳性率的比值比OR=8.400(95%CI:1.107~63.735,P0.05);药疹组与健康体检组HLA-B*5801基因阳性率的比值比OR=4.938(95%CI:1.056~23.100,P0.05)。结论别嘌呤醇引起发疹型药疹患者HLA-B*5801等位基因阳性率与对照组比较差异没有统计学意义,但与HLA-B*5801的基因携带具有相关性。     

柳州地区不同人群艾滋病及肝炎病毒感染的调查与研究

目的:了解柳州地区人类免疫缺陷病毒(HIV)及相关的肝炎病毒(HV)的感染状况.方法:应用酶联免疫-吸附法(ELISA)对柳州地区2107例不同人群进行抗-HIV、HBsAg、抗-HCV、抗-HDV、抗-HGV血清学检测.结果:经确证实验,在静脉吸毒者(IDUs)、性病及肝炎3组人群中检出抗-HIV阳性率分别为4.8%(10/208)、0.66%(2/304)、0.43%(2/462).14例HIV感染者与乙型、丙型、丁型、庚型肝炎病毒有不同模式的混合感染,其中1例HIV感染者4种类型肝炎病毒感染指标均为阳性.比较IDUs中1998年及1999年两次标本检测结果,HIV感染者增长4.6个百分点.结论:柳州地区特殊人群存在HIV感染;HIV感染有上升趋势;静脉吸毒及性传播是HIV及HV的主要传播途径;HIV与HV感染关系密切;不但存在HIV与HV的二重、三重、四重感染,并存在HIV与乙型、丙型、丁型、庚型HV的五重感染.     

凉山州彝族与其他民族社区人群艾滋病感染的影响因素分析

目的比较分析凉山州2011-2016年彝族与其他民族社区人群艾滋病哨点监测艾滋病病毒(HIV)感染的影响因素。方法采用多阶段分层抽样方法,抽取德昌、宁南、布拖3个县作为社区人群艾滋病监测哨点。采用问卷调查收集调查对象的人口学和行为学特征,并对研究对象进行HIV抗体的血清学检测。多因素非条件Logistic回归,分析彝族和其他民族人群感染HIV的危险因素。结果在2011-2016年凉山州3个哨点县,共监测社区哨点人群共14 198人,其中彝族共4 149人(29.22%),检出HIV抗体阳性197例,阳性检出率为4.75%;汉族及其他民族共10 049例(70.78%),检出HIV阳性30例,阳性检出率为0.30%。在彝族人群中,有吸毒史[比值比(OR)=6.69,95%可信区间(CI):4.23,10.56],高危临时性行为(OR=1.72,95%CI:1.03,2.87)和寡居(OR=2.03,95%CI:1.10,3.75)的个体,感染HIV的风险均较高。而女性与男性相比(OR=0.62,95%CI:0.45,0.85),小学(OR=0.52,95%CI:0.36,0.74)、初中(OR=0.48,95%CI:0.25,0.94)、高中及以上(OR=0.27,95%CI:0.08,0.85)与文盲相比,感染HIV的风险均较低。在汉族人群中,有吸毒史能增加HIV感染的风险(OR=26.11,95%CI:5.70,119.72)。结论凉山州彝族比汉族及其他民族有更高的HIV感染风险,彝族的性观念和习俗及较低的教育程度,成为导致凉山州HIV传播和流行的重要社会文化因素。     

少数民族与汉族注射吸毒人群艾滋病哨点监测结果分析

目的对比分析少数民族和汉族注射吸毒人群(IDUs)艾滋病监测结果,为综合干预提供依据。方法利用2009年和2010年攀枝花市艾滋病哨点监测资料,将IDUs按照"民族"分为汉族和少数民族,并对其艾滋病病毒(HIV)感染状况及相关行为进行分析。结果少数民族IDUs HIV感染率为25.8%(39/151),显著地高于汉族IDUs的8.7%(62/714)。相对于汉族IDUs,少数民族IDUs艾滋病知识知晓比例低(77.5%),共用针具比例高(40.4%),文化程度低(文盲和小学文化占79.5%),流动性大(外省户籍占25.8%),接受预防艾滋病服务比例低(最近一年接受社区药物维持治疗/清洁针具交换服务比例为37.7%、接受同伴教育比例为11.3%)。结论在扩大IDUs综合干预服务的基础上,应重点对少数民族IDUs采取教育、扶贫、艾滋病民族特色干预等综合措施。     

丽水市HIV感染长期不进展者HLA-A、HLA-B和HLA-DRB1基因多态性的研究

目的从基因水平了解丽水市艾滋病病毒(HIV)感染长期不进展者(LTNPs)与典型进展者(TPs)的人类白细胞抗原(HLA)-A、HLA-B和HLA-DRB1位点等位基因频率,比较两类人群的差异,初步探索保护性基因和易感基因。方法应用聚合酶链反应-序列特异性引物技术(PCR-SSP),对丽水市42例LTNPs和48例TPs进行HLA-A、HLA-B和HLA-DRB1等位基因分型。结果共鉴定出9个HLA-A等位基因,16个HLA-B等位基因,12个HLA-DRB1等位基因。HLA-A*02频率LTNPs组(44.05%)高于TPs组(20.83%)(P0.01),而A*11频率则是LINPs组(20.24%)低于TPs组(42.71%)(P0.01);HLA-B*40频率LTNPs组(17.86%)低于TPs组(28.13%)(P0.05);HLA-DRB*15频率LTNPs组(5.95%)低于TPs组(29.17%)(P0.01);LTNPs组HLA基因座纯合子频率(15.87%)低于TPs组(33.33%)(P0.01)。结论在该人群中,HLA-A*02等位基因可能与延缓艾滋病疾病进程相关,而HLA-A*11、B*40、DRB1*15可能加速艾滋病疾病进程。含HLA基因杂合子者对疾病显示出更好的抵御能力。     

HLA-B27亚型与强直性脊柱炎的相关性研究

目的:研究重庆地区汉族人群的正常人和强直性脊柱炎(AS)患者的HLA-B27亚型基因分布的特点,分析HLA-B27亚型与AS发生的相关性.方法:采用PCR-SSP方法对重庆地区汉族人群中HLA-B27阳性的正常人126例和AS患者134例进行HLA-B27亚型的检测.结果:在正常组和AS组中,共检出了10种HLA-B27亚型,2组均以B*2704和B*2705亚型为优势亚型,2亚型分别为90%和95%.2组间的B*2704和B*2707亚型的构成比差异有统计学意义.B*2704亚型在AS患者组中的分布大于正常组,B*2707亚型在正常组的分布大于AS患者组.结论:B*2704亚型与AS呈正相关(OR=2.12,P＜0.05),为重庆地区汉族人群中的主要致病基因,而B*2707亚型与AS呈负相关(OR=0.11,P＜0.05),可能有保护性作用.     

应用HLA-B~*5701等位基因药前筛查阿巴卡韦超敏反应

阿巴卡韦超敏反应(ABC HSR),是欧美国家临床应用抗艾滋病药物阿巴卡韦时,少数病例发生的过敏性多器官综合征,2001年发现,HLA-B*5701等位基因与阿巴卡韦超敏反应密切相关。发现这一基因位点后,诸多的研究致力于解决一个问题,即能否将HLA-B*5701等位基因筛查应用于临床,在阿巴卡韦用药前进行筛查,从而排除潜在的超敏反应患者,避免因服用阿巴卡韦带来的危害。文章综述了HLA-B*5701基因筛查从发现到临床应用所经历的发展过程,以及在国际上的研究现状。     

梧州汉族人群人类白细胞抗原-A、-B等位基因与α-地中海贫血的相关性研究

目的 探讨广西梧州汉族人群人类白细胞抗原(HLA)-A和HLA-B等位基因多态性与α-地中海贫血的关系.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126例汉族α-地中海贫血患者(病例组)和173名正常健康人(对照组)进行HLA-A和HLA-B基因多态性分析.通过等位基因频率和单倍型频率比较,计算α-地中海贫血发生的相对危险度(比值比,OR),分析HLA-A和HLA-B等位基因与梧州汉族人群地中海贫血发生的相关性.结果 病例组HLA-A*33:03、HLA-B*15:01、HLA-B*55:02等位基因频率[15.48％(39/252)、3.17％(8/252)、6.75％(17/252)]显著高于对照组[9.83％(34/346)、0.29％(1/346)、2.31％(8/346)],OR值分别为1.68、11.31、3.06(P均＜0.05);HLA-B*15:02等位基因频率[7.54％(19/252)]显著低于对照组[12.72％(44/346)],OR值为0.56(P＜ 0.05).HLA-A*11:01-B*55:02、HLA-A*02:07-B*40:01单倍型频率[2.38％(6/252)、1.59％(4/252)]显著高于对照组[0.29％(1/346)、0.00％(0/346)],OR值分别为8.41、11.16(P均＜0.05).结论 HLA-A和HLA-B等位基因具有多态性.HLA-A*33:03、HLA-B*15:01、HLA-B*55:02、HLA-B*15:02等位基因发生频率和HLA-A*11:01-B*55:02、HLA-A*02:07-B*40:01单倍型发生频率与梧州汉族α-地中海贫血的易感性有关联.     

台山市2006年艾滋病自愿咨询检测情况分析

目的了解在台山市疾病预防控制中心艾滋病自愿咨询检测(VCT)室求询的人群及艾滋病病毒(HIV)抗体阳性者的情况,为进一步开展VCT服务,阻断HIV传播提供依据。方法用统一的VCT表格记录咨询个案,对咨询个案和阳性个案进行分析。结果在有完整记录的166个求询者中,15～49岁青壮年占84.9%,求询者类型主要为异性性接触、静脉吸毒和HIV感染者的家属。126人接受免费检测共发现HIV抗体阳性者32人,阳性率25.4%。HIV感染者主要是静脉吸毒者和感染者的配偶。结论台山市疾控中心在高危人群中推行VCT对发现HIV感染者或AIDS病人效率较高。青壮年吸毒人群和HIV感染者家属是艾滋病高危人群,也是开展VCT,实施行为干预的重点人群。     

Introduction of pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 variant in Polish HIV‐infected patients

Objective

Prospective pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 allele can significantly reduce the number of cases of abacavir‐related hypersensitivity among HIV‐infected patients treated with this drug. The aim of this study was to establish the frequency of the HLA B*5701 variant in HIV‐infected Poles.

Methods

The sequence‐specific primer (SSP) test was used to assess the feasibility of the introduction of such testing in clinical practice. For this purpose, 234 randomly selected HIV‐positive patients were screened using a low‐resolution SSP assay, with HLA B*5701‐positive results confirmed using a high‐resolution test.

Results and Conclusions

The HLA B*5701 variant was found in 11 of 234 subjects (4.7%). Testing with the selected method proved quick and reliable.

     

Value of the HLA-B*5701 allele to predict abacavir hypersensitivity in Spaniards

The use of abacavir (ABC) may be associated with a hypersensitivity reaction (HSR) that requires discontinuation of the drug. The HLA-B*5701 allele has been linked to this HSR. Information on the strength of this association across distinct geographic regions and ethnicities is scarce. We tested HLA-B*5701 in 53 Spaniards infected with HIV who received ABC treatment. The presence of HLA-B5701 had strong positive and negative predictive values for ABC HSR, 92% and 63%, respectively.     

HLA-B*5701 frequency n Chilean HIV-infected patients and in general population

It has been demonstrated that HLA-B*5701 screening reduces the risk for hypersensitivity reaction to abacavir in HIV-infected patients. Since B*5701 prevalence varies among different populations, it is important to determine the carrier frequency prior to its use for the screening of HIV-infected patients. The aim of this study was to determine HLA-B*5701 carrier frequency in Chilean general population and HIV-infected patients referred for B*5701 typing. For that purpose 300 blood bank donors and 492 abacavir-naïve HIV-infected patients from Chile were screened for B*5701 by a sequence specific primer PCR. We detected 14/300 (4.7%) B*57-positive individuals in the Chilean general population, 11 (3.7%) were B*5701 positive, and 3 (1%) had another subtype. All were heterozygous, thus a B*5701 allele frequency of 2% was determined. Eleven of 492 (2.2%) HIV-patients carried a B*5701 allele. The difference between these frequencies is probably due to slow progression of HIV infection in HLA-B*5701 carriers, thus less patients would require antiretroviral therapy and B*5701 typing. Considering the usefulness of B*5701 screening, its prevalence in the Chilean general population, and the availability of a validated method, we conclude that HLA-B*5701 typing in Chilean HIV-infected patients about to initiate abacavir treatment is strongly recommended.     

Prospective epidemiological study of the prevalence of human leukocyte antigen (HLA)‐B*5701 in HIV‐1‐infected UK subjects

Objectives

Human leukocyte antigen (HLA)‐B^*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC) in White and Hispanic subjects. Across the UK, limited data exist on HLA‐B^*5701 prevalence in HIV‐1‐infected subjects. We determined HLA‐B^*5701 prevalence in the general HIV‐1‐infected population and in specific ethnic groups, particularly Black Africans who, in general, exhibit greater genetic diversity. We also compared HLA‐B^*5701 results obtained from local laboratories with those from a central provider.

Design and methods

Multi‐centre, observational study. All HIV‐1‐infected adult individuals receiving care at participating centres were eligible, irrespective of treatment status or prior exposure to ABC. Subjects provided samples for HLA‐B^*5701 assessment by both local (blood) and central laboratories (buccal swabs). HLA‐B^*5701 prevalence was adjusted to represent the ethnic group composition of the general UK population, and by main ethnic group.

Results

From eight UK centres, 1494 subjects [618 (41%) White, 770 (52%) Black] were recruited. Eighty‐nine per cent of Black subjects reported an immediate country of origin in Africa. Overall adjusted HLA‐B^*5701 prevalence was 4.55% [95% confidence interval (CI) 3.49% to 5.60%]. Among White subjects, prevalence was 7.93% (CI 5.80% to 10.06%). Among Black subjects, only two (both Ugandan) were HLA‐B^*5701 positive giving a rate of 0.26% (CI 0.07% to 0.94%).

Conclusions

HLA‐B^*5701 prevalence was similar to previously reported rates in White HIV‐infected subjects but considerably lower than that reported in Black HIV‐1‐infected subjects, as a result of the large proportion of Black African subjects.     

Prospective HLA-B*5701 screening and abacavir hypersensitivity: a single centre experience

Suspected hypersensitivity is the main reason for the early discontinuation of abacavir. After the observation that the risk of hypersensitivity correlated with ethnicity, the presence of the HLA allele B5701 was found to be the strongest retrospective predictor of hypersensitivity. Two prospective cohorts have since demonstrated a significant reduction in abacavir hypersensitivity rates with the use of prospective human leukocyte antigen screening. We describe our experience of prospective HLA-B5701 testing and the impact on rates of abacavir hypersensitivity.     

First large, multicenter, open-label study utilizing HLA-B*5701 screening for abacavir hypersensitivity in North America

A hypersensitivity reaction is associated with abacavir in approximately 2-8% of exposed patients. The frequency of the HLA-B*5701 allele varies across racial groups and significantly correlates with risk of hypersensitivity. Studies in Europe and Western Australia demonstrated that prospective screening can significantly reduce the rate of hypersensitivity by avoiding the use of abacavir in patients carrying the HLA-B*5701 allele. Prospective HLA-B*5701 screening in a large, racially diverse North American population resulted in less than 1% of individuals diagnosed with a suspected abacavir hypersensitivity reaction (ABC HSR) and no positive skin patch test through 30 weeks among HLA-B*5701-negative individuals.