先天畸形及代谢缺陷

052437内蒙古地区繁汉族儿童正常人群HLA-DRB1基因多态性研究/孙广…//中国基层医药.-2005,12(2).-129～130结果:1.蒙、汉族HLA—DRB1各等位基因均被检出;2.蒙古族HLA—DRB1基因频率较高的依次是*040x(14.9%)、*120x(13.7%)和*150x(10.3%),而较低的等位基因依次是:*1001(2%)、160x(2%)和010x(3.5%);汉族HLA—DRB1基因频率较高的等位基因依次是:*0901(15%)、150x(13.4%)和*040x(11.8%),而较低的等位基因依次是:*1001(3.8%)、*070x(4.2%)和*160x(4.     

异基因造血干细胞移植治疗儿童再生障碍性贫血临床分析

目的探讨异基因造血干细胞移植在儿童再生障碍性贫血治疗中的作用。方法10例再障患儿中,5例行HLA相合同胞供者异基因外周造血干细胞移植,3例行无关供者异基因外周造血干细胞移植,1例行无关供者骨髓移植,1例行脐血移植。结果1例接受脐血移植者未植活,其余9例均植入。中位植入时间14d（8～24d）,中性粒细胞〉0.5×10^9/L中位时间12d（8～19d）,血小板〉20×10^9/L中位时间17d（9～40d）。2例发生排斥,1例接受了第二次移植,1例移植后3个月血象开始自行恢复。结论如有HLA相合的同胞供者,异基因造血干细胞移植可作为儿童再障的一线治疗;临床重症感染无法控制的患儿,并非移植绝对反指征,相反可通过移植后的造血重建控制感染。     

单倍体相合造血干细胞移植

目前,异基因造血干细胞移植(allo-HSCT),已成为治疗多种血液及非血液系统疾病主要手段之一.对于那些没有HLA完全相合供者的患者单倍体相合造血干细胞移植(haploidentical hematopoietic stem cell transplantation)不失为一种好方法.什么是单倍体相合?人体细胞都是二倍体细胞(为双链DNA),只有生殖细胞为单倍体(为单链DNA).     

广西壮、汉族哮喘儿童人类白细胞抗原-B、-DR基因的多态性

目的 探讨广西壮、汉族人类白细胞抗原(HLA)-B、-DR位点的基因多态性与儿童哮喘发病的关联性.方法 将3代居住广西南宁地区无血缘关系的84例哮喘儿童(汉族57例,壮族27例)和168例无哮喘和特应性疾病的健康人(汉族83例,壮族85例)纳入研究.所有哮喘儿童应用强生法玛西亚系统检测其血清总IgE水平、10种吸入性变应原皮肤点刺试验和肺功能检测.利用基因芯片法检测HLA-B的40个和HLA-DR的26个等位基因.分别计算汉族和壮族人群中哮喘和健康对照组基因频率,进行x2检验,分别比较组间基因频率差异和危险性分析,计算基因与哮喘的关联强度比值比(OR值).结果 HLA-B位点共检出27个等位基因,HIA-DR检出21个等位基因.HLA-B46、HLA-DRB1～0.983)、7.885(0.896～69.399)和2.782(1.188～6.516),且HLA-DR B1*070X等位基因在本组壮族人群中未见出现.壮族人群中,HLA-B56、-861和-DRB1*1001等位基因在哮喘与健康对照组间有分布差异,哮喘与健康对照组比较有显著差异,组间HLA-B56经x2检验有统计学意义(x2=6.588 P<0.01),HLA-DRB1*1001经Fisher精确概率法检验有统计学意义(P=0.043);HLA-B56和HLA-DRB1*1001的OR值(95%CI)分别为9.432(1.713～51.932)和10.50(1.044～105.590).而HIA-B61等位基因在壮族哮喘患者中未见出现.结论 HLA-B和HLA-DR的基因多态性在壮、汉族间分布有差异;HLA-B56和HLA-DRB1*1001等位基因可能为壮族人群的哮喘易感基因;而汉族人群中HLA-DRB1*070X和HLA-DRB1*11XX等位基因是易感基因,HLA-B46等位基因可能为保护基因.*070X和HLA-DRB1*11XX等位基因仅在汉族的哮喘与健康人群分布有差异,哮喘与健康对照组比较有显著差异(Pa<0.05),OR值(95%CI)分别为0.388(0.153     

内蒙古西部地区汉族新生儿呼吸窘迫综合征与SP-B外显子7区域R236C位点的相关性研究

目的通过检测和分析肺表面活性物质蛋白B基因外显子7(exon7)区域上是否存在基因变异,探讨其与内蒙古西部地区汉族新生儿呼吸窘迫综合征(NRDS)发病的关系。方法采用病例对照研究方法,选择祖上三代都居住在内蒙古西部地区的汉族NRDS患儿47例作为病例组,选择同民族和同群体中未发生NRDS的新生儿47例为对照组。通过PCR基因分析技术检测SP-B基因外显子7区域上有无突变,以及SP-B外显子7(R236C)位点的基因型、等位基因分布。结果在内蒙古西部地区汉族新生儿中,SP-B基因外显子7区域无突变发生;SP-B外显子7(R236C)位点基因型均可检出两种基因型(CC、CT),两组中均未检出TT基因型。病例组CC和CT基因型频率分别为72%和28%,C等位基因频率为85%,T等位基因频率为15%。对照组此两种基因型分别为85%和15%,C等位基因频率为93%,T等位基因频率为7%。病例组与对照组此位点基因多态性相比等位基因及基因型频率在两组之间差异无统计学意义(P0.05)。结论内蒙古西部地区汉族NRDS患儿的SP-B基因第7外显子未发现基因突变。未发现SP-B基因外显子7(R236C)位点基因多态性与该地区汉族NRDS的发生有明显相关性。     

武汉汉族新生儿肺表面活性物质蛋白B基因多态性频率分布

目的了解武汉汉族新生儿肺表面活性物质蛋白B(SP-B)基因多态性频率分布。方法采用PCR-限制性片段长度多态性分析技术和基因测序技术对武汉汉族新生儿286例(男205例,女81例)进行SP-B 1580C/T位点基因型频率检测,并将武汉汉族新生儿SP-B 1580C/T等位基因频率与德国高加索人、美国白种人及日本人比较。结果武汉汉族新生儿SP-B 1580位点基因型CC、CT、TT频率分别为44.8%、47.6%和7.6%,等位基因C和T频率分别为68.5%和31.5%;不同性别、出生体质量、胎龄新生儿SP-B 1580位点的基因型及等位基因频率比较均无统计学差异。武汉汉族新生儿SP-B 1580等位基因频率与德国高加索人和美国白种人相比均有统计学差异(Pa<0.01),但与日本人比较差异无统计学意义。结论武汉汉族新生儿SP-B 1580基因型及等位基因频率在不同性别、出生体质量、胎龄中无明显关联。不同种族人群SP-B 1580C/T基因多态性分布存在明显差异。     

儿童系统性红斑狼疮与人类白细胞抗原-A、B、DR等位基因的相关性研究

目的　研究儿童系统性红斑狼疮 (SLE)与人类白细胞抗原 (HLA) A、B、DR等位基因的相关性。方法　对 5 3例SLE患儿及 78例正常对照儿童 ,应用微量淋巴毒实验和聚合酶链反应结合序列特异性多态性 (PCR SSP)分析方法分别行HLA Ⅰ类抗原及HLA Ⅱ类基因检测。结果　发现SLE患儿HLA Ⅰ类抗原A9、A11、B5、B17较正常对照儿童升高 ,与SLE发病相关。HLA Ⅱ类基因DRB1 15、DRB1 0 3基因频率较正常对照儿童明显增高 ,与SLE发病相关。而DRB1 0 4基因频率明显降低 ,为疾病保护基因。其中 ,HLA基因的型别不同 ,可影响SLE的临床表现 ,狼疮肾炎主要与HLA DRB1 0 3基因相关 ,而DRB1 15则与各型SLE相关。结论　系统性红斑狼疮患儿携带HLA A9、A11、B5、B17、HLA DRB1 15、DRB1 0 3基因与SLE易感有关。其中HLA型别不同 ,影响SLE患儿的临床表型。DRB1 0 4基因频率降低 ,为疾病保护性基因     

造血干细胞移植治疗原发性免疫缺陷病进展

异基因造血干细胞移植(HSCT)是根治部分原发性免疫缺陷病(PID)的重要甚至惟一手段。人类白细胞抗原(HLA)全相合的同胞供者移植后PID患者的长期存活率可达90%以上。国际上重症联合免疫缺陷病(SCID)移植后的长期存活率在70%以上,Wiskott-Aldrich综合征患者移植后的总体存活率在80%以上,慢性肉芽肿病患者接受HLA全相合移植后长期存活率可达90%以上。预处理方案是决定HSCT成功与否的重要因素,移植物抗宿主病及巨细胞病毒的复燃严重影响患者干细胞移植后的存活率及生活质量。文章对近年HSCT治疗PID患者在非HLA全相合同胞供者移植、预处理方案、移植物抗宿主病的防治、巨细胞病毒复燃的防治方面的进展进行介绍。     

蒙、汉族儿童原发性肾病综合征TIM-3基因及IFN-γ检测的意义

目的研究TIM-3基因多态性及γ干扰素(IFN-γ)水平与儿童原发性肾病综合征(PNS)发病的相关性。方法采用病例对照研究,选取汉族PNS患儿21例,蒙古族(祖籍三代以上均为蒙古族)、汉族(祖籍三代以上均为汉族)健康体检各20例为对照组;采用PCR–限制性片段多态性分析方法,分析检测PNS患儿和对照组的T细胞免疫球蛋白黏蛋白分子3(TIM-3)基因外显子-574 A/C的单核苷酸多态性,比较基因型及等位基因频率;采用酶联免疫吸附法检测血IFN-γ水平,并分析其变化。结果汉族和蒙古族正常对照组之间TIM-3基因外显子-574A/C位点基因型(AA、AC、CC)分布差异无统计学意义(P=0.741);两组间等位基因频率差异也无统计学意义(P=0.655)。将汉族和蒙古族正常对照组合并与汉族PNS患儿进行比较,汉族PNS患儿-574A/C位点AA、AC和CC基因型频率分别为9.52%、28.57%和61.90%,与40例正常对照组儿童的基因型分布差异有统计学意义(P=0.017);汉族PNS患儿的C等位基因频率为76.2%,高于正常对照组(50.0%),差异有统计学意义(P=0.005),与A等位基因个体比较,C等位基因携带者儿童发生PNS的风险增加3.20倍(95%CI:1.39~7.37)。汉族PNS、汉族以及蒙古族正常对照组之间血清IFN-γ水平的差异无统计学意义(P0.05)。结论 TIM-3基因外显子-574A/C的单核苷酸多态性可能与儿童PNS的发病相关;IFN-γ与儿童原发性肾病综合征的发病无明显相关性。     

天津地区汉族Graves病患儿人类白细胞抗原-DQB1基因多态性

目的 检测天津地区汉族儿童Graves病(GD)人群的人类白细胞抗原(HLA)-DQB1基因,分析其易感基因,并观察家族性GD与散发性GD之间HLA-DQB1基因的差异.方法 采用PCR-序列特异性引物方法检测天津地区40例汉族GD患儿及50例健康儿童HLA-DQB1基因型,计算和比较各组间等位基因出现频率,并应用SPSS 11.5软件进行统计学分析.结果 1.GD组HLA-DQB1*0303基因分布频率与健康对照组比较明显增高(χ2=9.097,P=0.003);2.家族性GD组HLA-DQB1*0301基因频率分布与散发性GD组比较明显升高(χ2=9.724,P=0.002);3.DQB1*02、DQB1*0302等位基因频率比较差异均无统计学意义(P=0.953,0.414,0.902).结论 DQB1*0303基因是天津地区汉族儿童GD的易感基因,具有此基因者易患GD,而有GD家族史的儿童具有DQB1*0301基因也易患GD.     

Association of <Emphasis Type="Italic">HLA-B*08:DRB1*03</Emphasis> with Immunoglobulin A-deficiency

Objective Susceptibility to IgA deficiency (IgAD) is strongly associated with alleles of HLA, but it is not equally strong in different human populations. Therefore, the goal of this study was to determine the HLA-A,-B and-DRB1 antigenic and haplotypic frequencies in unrelated Polish Caucasian IgA-deficient patients who had never been examined so far in this respect. Methods The HLA alleles were determined by means of low resolution polymerase chain reaction with sequence specific primers (PCR-SSP) method in a group of IgA-deficient patients and control subjects from the same area. Results The HLA-DRB1*03 allele showed the strongest association with IgA deficiency in the Polish population (OR=6.6, p_cor=0.0084). The HLA-B*08 allele was also associated with predisposition to the disease (OR=6.22, p_cor=0.033). These significant associations could be explained in the context of a positive association of IgAD with the HLA-B*08:DRB1*03 haplotype, previously reported in other Caucasoid populations from Northern and Central Europe. In our group the HLAB*08:DRB1*03 haplotype was present in 52.9% of IgA-deficient patients comparing to 9.9% in controls (p<0.00011). A positive association of HLA-B*08 and DRB1*03 was stronger in IgA-deficient males than in females from the same group. Conclusion Immunoglobulin A deficiency in Polish population is strongly associated with HLA-B*08:DRB1*03 haplotype rather than with single alleles.     

Polymorphisms of Human Leukocyte Antigen Genes in Korean Children with Kawasaki Disease

Background Kawasaki disease is a leading cause of acquired heart disease in children. The prevalence rate varies in different ethnic groups. Recently, with the clinical application of molecular genetic technology, human leukocyte antigen (HLA) polymorphisms associated with several diseases have been identified by DNA analysis. This study aimed to assess the association of HLA alleles with susceptibility and complications of Kawasaki disease in Korean children. Methods In this study, DNA was extracted from 74 children with a diagnosis of Kawasaki disease. The polymorphisms of the HLA-A, -B, -C, and -DRB1 alleles of patients with Kawasaki disease were determined by polymerase chain reaction (PCR)–amplification refractory mutation system (ARMS) and PCR–sequence-specific primer (SSP) analysis. The polymorphisms identified were compared with those of 159 normal healthy control subjects. Results There was a significant increase in the frequencies of the HLA-B35, -B75, and -Cw09 alleles in patients with Kawasaki disease compared with the healthy control group. There was no increase in the frequency of HLA-DRB1 alleles among the Kawasaki disease patients compared with a healthy control group. When the patients with Kawasaki disease were divided into two subgroups, with or without coronary complications, the Kawasaki disease patients with coronary complications showed a significantly increased frequency of the HLA-DRB1*11 allele compared with the healthy control group and increased frequency of HLA-DRB1*09 in a comparison of the subgroups. Conclusions This study suggests that polymorphisms in some alleles of B and C in HLA class I genes are associated with Kawasaki disease in Korean children.     

Unrelated cord blood transplantation for second hemopoietic stem cell transplantation

BACKGROUND: The Kanagawa Cord Blood Bank (KCBB) reports the treatment of 12 patients who received umbilical cord blood transplantation (CBT) from unrelated donors as their second hemopoietic stem cell transplantation (HSCT). METHODS: Provided by the KCBB, between February 1997 and September 2000, 12 patients had unrelated CBT as a second HSCT. Six patients were male and six female; nine patients were in malignant, and three were in non-malignant conditions. The median age of the patients was 7.9 years (range, 2.2-28.0), and the median bodyweight was 22.5 kg (12.0-55.0). The HLA-A and -B serological and DR genotypical disparities between the patients and CBT donors were as follows: one patient was a 0-mismatch, six were 1-mismatches, and five were 2-mismatches. RESULTS: The median time between first and second HSCT was 14.0 months (1.0-47.0). The overall survival rate was 25.0%, three years after CBT (Kaplan-Meier estimate). Mortality after CBT as a second HSCT accounted for nine cases, six from infection and three from treatment-related mortality other than infection. CONCLUSION: Cord blood transplantation offers the advantage of rapid availability, absence of donor risk, and possibly less HLA restriction. In these contexts, unrelated CBT should be considered as a source of HSCT for a second transplant.     

Immunogenetic heterogeneity in single-system and multisystem langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare disease with an unknown etiology and poorly understood pathogenesis. Immunologic, viral, and proliferative clonality causes have all been considered. To determine whether Langerhans cell histiocytosis and its two main subgroups, single-system and multisystem disease, are associated with HLA-A, -B, -Cw, or -DR alleles, a total of 84 patients <15 y of age at the time of diagnosis and of Nordic origin were analyzed, 82 for HLA class I and 76 for HLA class II. Stratification of the patients into two subgroups, single-system disease (skin only, and monostotic and polyostotic disease) and multisystem disease with or without organ dysfunction, showed that patients with single-system disease (17 of 45, 38%) more often (p = 0.00018 and, after correction, p = 0.029) had the phenotype HLA-DRB1*03 compared with patients with multisystem disease (1 of 31, 3%). In the patients with multisystem disease a nonsignificant reduction of the frequency of this phenotype was seen compared with controls (p = 0.02, uncorrected). In 14 of the patients with single-system disease, but none with multisystem disease, the deduced haplotype HLA-A*01, B*08, DRB1*03 was found. High-resolution typing, performed in nine patients, revealed that all had the HLA-A*0101, B*0801, DRB1*0301, DQB1*0201 alleles. Our findings suggest an immunogenetic heterogeneity in the two clinical entities of Langerhans cell histiocytosis and indicate that HLA-DRB1*03 may play a protective role against developing multisystem disease. Further studies to confirm these findings are desired.     

Donor selection process for allogeneic hematopoietic stem cell transplantation at the university hospital of Düsseldorf (1997-1998).

BACKGROUND: Transplantation of hematopoietic stem cells (HSC) is an effective treatment for a number of patients with life-threatening hematologic diseases. HSC donors can be found in the family of the patient or in registries of unrelated donors. In the present study, the search procedure within the last two years for an allogeneic HSC donor at the University of Düsseldorf is analyzed. PATIENTS AND METHODS: During 1997 and 1998, an early search for a related HSC donor in the family was performed for 70 high risk pediatric patients. During the same period, the search for an unrelated HSC donor for 116 adult and pediatric patients was performed. Low resolution HLA-A and -B typing was performed by serology in combination with DNA-typing. High resolution typing of HLA-A, -B and -C was carried out by DNA-sequencing. Low resolution HLA-DRB- und HLA-DQB1-typing was done solely by DNA-typing and high resolution typing of these genes was performed by DNA-sequencing. MAIN RESULTS: For 51 of 70 high risk pediatric patients (73%), no family donor could be defined, 16 of 70 patients (23%) had a genotypically identical sibling and for three of 70 patients (4%) an HLA-acceptable donor in the extended family could be identified. The search for an unrelated HSC donor was successful in 74% of the adult and pediatric patients lacking such a family donor. Most noteworthy, nearly all of the HLA-acceptable donors were identified from that group of donors in the registries, which were not only HLA-A and HLA-B, but also HLA-DR pretyped. CONCLUSION: These data show, that a growing number of pediatric patients with high risk leukemia need an unrelated HSC donor and that HLA-ABDR-pretyped registries present the optimal prerequisite to identify an HSC donor for most of the patients. In addition, 25% of the patients with no family or unrelated HSC donor require HSC transplants from alternative donors like unrelated Cord Blood (CB) from high quality cord blood banks.     

HLA-B5 and B21 antigens in aortoarteritis

The distribution of class I HLA antigens (HLA-A, B) were determined in 50 patients of Aortoarteritis in an Indian population. This included 29 females and 21 males. The difference in antigen frequency was observed between patients and controls with reference to HLA-A19, B5 and B21 antigens. A decreased frequency of HLA-A19 was observed in the patients as compared to controls (14% vs 33.25%, X²=6.81, P<0.025). Of the B locus antigens, an increased frequency of HLA B5 was observed in the patients as compared to controls (48% vs 29.5%, X²=6.2, P<0.025). HLA-B21 was also increased in the patients as compared to the controls (18% vs 6.5%, X²=6.67, P<0.025). These data suggest the involvement of genetic factor (s) in the aetiopathogenesis of this disease. Further, the observations indicate that HLA-B5 and B21 may be associated with Aortoarteritis.     

Lead levels in women at delivery at the Muhimbili National Hospital: a public health problem

Lead poisoning is a global health problem but unrecognized in African countries. Umbilical Cord Lead levels can be used to determine community exposure to lead. At delivery, 150 women were recruited for cord blood lead. A prevalence of 10% beyond the accepted range was found. Cord blood levels ranged from 0.1-18.1 microg/dl, with a mean of 4.1 microg/dl. There was no association between lead levels and pregnancy outcomes in terms of low birth weight and pre-term delivery. There was a weak association between lead poisoning and living in a painted house and use of tap water (OR = 1.4). There was no association between lead poisoning and use of facial cosmetics. Living near heavy traffic was more associated with increased cord blood lead levels.     

Genetic analyses of thiopurine methyltransferase polymorphisms in Greenlandic and Danish populations

AIM: To determine the frequency of thiopurine methyltransferase (TPMT) low-activity alleles in the Greenlandic and Danish populations. METHODS: 142 Greenlandic individuals and 200 Danish blood donors were screened for the TPMT G460A and A719G low-activity alleles. RESULTS: Thiopurine methyltransferase low-activity alleles were significantly higher in the Greenlandic compared to the Danish population, being 8.1% (95% CI 4.9-11.3) and 3.5% (95% CI 1.7-5.3) (p<0.01), respectively. Except for one Danish patient with an A719G allele (TPMT*3C), all the aberrant alleles were compound G460A and A719G alleles (TPMT*3A). CONCLUSION: In the Danish population, the incidence of thiopurine methyltransferase low-activity alleles was found to be similar to other Caucasian populations previously described. In contrast, the Greenlandic population showed a significantly higher frequency of thiopurine methyltransferase low-activity alleles.     

幼年特发性关节炎患儿HLA-DRB1基因多态性分析

目的：研究广东地区汉族幼年特发性关节炎（JIA）患儿HLA-DRB1位点等位基因多态性分布特点。方法：采用序列特异性引物-聚合酶链反应(SSP-PCR)技术对94例JIA患儿和226例健康儿童HLA-DRB1的13个等位基因进行分析,并分析上述基因在各组中的分布。结果：JIA患儿HLA-DRB1*08(P=0.0014,OR=2.26)的分布频率明显高于健康儿童,HLA-DRB1*12（P=0.032,OR=0.55）的分布频率明显低于健康儿童。在JIA全身型及多关节型中HLA-DRB1*08明显增高,而HLA-DRB1*15在JIA全身型及少关节型中明显降低,观察组与对照组比较P<0.05,差异有统计学意义,其他各位点差异无统计学意义。结论： HLA-DRB1*08可能是JIA小儿的易感基因。HLA-DRB1*12可能是JIA小儿的保护基因,其中HLA-DRB1*08是全身型及多关节型的易感基因,而HLA-DRB1*15与全身型及少关节型保护基因密切相关。［中国当代儿科杂志,2010,12（5）：333-337］     

儿童系统性红斑狼疮与HLA基因单倍型和基因型的相关性及家系分析

目的 探讨HLA基因连锁不平衡情况对儿童SLE发病的影响,以期发现HLA基因在SLE发病中的作用。方法 53例SLE患儿,其中40例有父母资料,35例HLA-DRB*15阳性的SLE患儿,其中有父母资料者27例,78名健康对照儿童,43名有父母资料,及1个SLE大家系作为研究对象,应用微量淋巴毒实验,序列特异性引物聚合酶链反应方法,分析了研究对象的HLA-I类抗原A、B位点,HLA-Ⅱ类基因。DRBI位点的多态性。根据实测的单倍型及基因型情况与正常对比,分析了SLE患儿与HLA-A、B、DR单倍型及基因型的相关性,并分析了DRB1*15阳性的SLE患儿其DRB1*15基因来自父母的垂直传递情况。结果 (1)患儿比正常对照单倍型种类少,患儿与对照共有单倍型较少。单倍型A9B40DRB1*15频率在SLE患儿中较对照高,SLE大家系的研究中,也恰恰表现为A9B40DRB1*15单倍型与患病相连锁。(2)SLE患儿基因型以DRB1*09／DRB1*15及DRB1*03／。DRB1*15多见。(3)在父母携带DRB1*15基因相同的情况下,SLE患儿的DRB1*15基因来源于父亲者较正常对照多。结论 SLE发病不仅与单个HLA基因有关,而且与HLA的某些基因组合相关,由此可见SLE多发位点的致病作用有叠加性。SLE患儿DRB1*15来自父亲者较对照组多,其机理及意义尚不清楚,可能与HLA的遗传模式有关。