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The role of the selenoprotein S (SELS) gene -105G>A promoter polymorphism in inflammatory bowel disease and regulation of SELS gene expression in intestinal inflammation. 硒蛋白S (selenoprotein S, SELS)基因-105G>A启动子多态性在炎症性肠病中的作用以及SELS基因在肠道炎症中的表达调控
Pub Date : 2007-08-01 DOI: 10.1055/S-2007-988408
J. Seiderer, J. Dambacher, B. Kühnlein, S. Pfennig, A. Konrad, H. Török, D. Haller, B. Göke, T. Ochsenkühn, P. Lohse, S. Brand
Recently, a -105G>A promoter polymorphism coding for selenoprotein S (SELS) has been shown to increase proinflammatory cytokine expression. We, therefore, analyzed SELS expression and potential phenotypic consequences of the -105G>A polymorphism in patients with inflammatory bowel disease (IBD). SELS mRNA was measured by quantitative polymerase chain reaction (PCR) in intestinal epithelial cells (IEC) after stimulation with proinflammatory cytokines and in human colonic biopsies of IBD patients as well as in murine models of ileitis and murine cytomegalovirus (MCMV) colitis. Genomic DNA from 563 individuals (Crohn's disease: n = 205; ulcerative colitis: n = 154; controls: n = 204) was analyzed for the presence of the SELS-105G>A polymorphism and the three nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/caspase recruitment domain-containing protein 15 (CARD15) variants p.Arg702Trp, p.Gly908Arg and p.Leu1007fsX1008. SELS mRNA expression was increased in IEC after stimulation with proinflammatory cytokines, while its expression was not significantly altered in murine ileitis and MCMV colitis and in inflamed ileal and colonic lesions in IBD patients compared with normal controls. The SELS-105G>A polymorphism was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype or serum tumor necrosis factor alpha (TNF-alpha) levels in these patients. Medium serum TNF-alpha was 1.27 pg/ml in IBD patients, while none of the controls had TNF-alpha concentrations above the detection threshold (P < 0.0001). SELS mRNA expression is upregulated by proinflammatory cytokines in IECs but the SELS-105G>A polymorphism is not associated with IBD susceptibility and does not contribute to a certain disease phenotype or increased TNF-alpha levels in IBD patients.
最近,硒蛋白S (selenoprotein S, SELS)编码的-105G> a启动子多态性已被证明可增加促炎细胞因子的表达。因此,我们分析了炎症性肠病(IBD)患者中-105G>A多态性的SELS表达和潜在表型后果。采用定量聚合酶链反应(PCR)检测促炎细胞因子刺激后肠上皮细胞(IEC)、IBD患者结肠活检以及小鼠回肠炎和小鼠巨细胞病毒(MCMV)结肠炎模型中SELS mRNA的表达。563人的基因组DNA(克罗恩病:n = 205;溃疡性结肠炎:154例;对照:n = 204)分析了SELS-105G>A多态性和三个核苷酸结合寡聚结构域含蛋白2 (NOD2)/caspase募集结构域含蛋白15 (CARD15)变体p.a arg702trp、p.g gly908arg和p.l u1007fsx1008的存在。促炎细胞因子刺激后,SELS mRNA在IEC中的表达增加,而在小鼠回肠炎和MCMV结肠炎以及IBD患者炎症回肠和结肠病变中的表达与正常对照组相比无显著变化。在IBD患者和对照组中观察到sel - 105g >A多态性的频率相似,并且与这些患者的某种疾病表型或血清肿瘤坏死因子α (tnf - α)水平无关。IBD患者中血清tnf - α浓度为1.27 pg/ml,而对照组中tnf - α浓度均未高于检测阈值(P < 0.0001)。在iec中,促炎细胞因子上调了SELS mRNA的表达,但SELS- 105g >A多态性与IBD易感性无关,也不会导致IBD患者的某种疾病表型或tnf - α水平升高。
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引用次数: 41
Abstracts of the 21st European Immunogenetics and Histocompatibility Conference. Barcelona, Spain. May 5-8, 2007. 第21届欧洲免疫遗传学和组织相容性会议摘要。西班牙巴塞罗那。2007年5月5日至8日。
Pub Date : 2007-05-01 DOI: 10.1111/j.1399-0039.2007.00836.x
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引用次数: 0
CD31/PECAM-1 genotyping and haplotype analyses show population diversity. CD31/PECAM-1基因分型和单倍型分析显示群体多样性。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00722.x
F-M Robbins, R J Hartzman

Using direct sequencing of complementary DNA products, the sequences of human CD31 from exon 1 through exon 16 of 179 individuals (139 unrelated) were systematically examined. Of the 14 biallelic single nucleotide polymorphic sites detected, 7 polymorphic sites involved amino acid substitution. These 14 polymorphic sites yielded 18 observed CD31 alleles and 9 predicted CD31 polypeptide sequences. Based on molecular haplotyping and family pedigree analysis, linkage disequilibrium among some single nucleotide polymorphic sites was observed. Single nucleotide polymorphism frequencies between populations were also measured using dot-blot hybridization with DNA or peptide nucleic acid probes.

利用互补DNA产物的直接测序,系统检测了179例(139例无亲缘关系)人CD31外显子1至外显子16的序列。在检测到的14个双等位基因单核苷酸多态性位点中,7个多态性位点涉及氨基酸取代。这14个多态性位点产生了18个CD31等位基因和9个预测CD31多肽序列。通过分子单倍型和家系分析,发现部分单核苷酸多态性位点存在连锁不平衡。群体间的单核苷酸多态性频率也用DNA或肽核酸探针进行点杂交测定。
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引用次数: 12
Childhood asthma and human leukocyte antigen type. 儿童哮喘与人类白细胞抗原类型。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00719.x
Y J Juhn, H Kita, L A Lee, R W Smith, S M Bagniewski, A L Weaver, V S Pankratz, R M Jacobson, G A Poland
Little is known about the relationship between human leukocyte antigen (HLA) class II genes and family history of asthma or atopy in relation to the incidence of childhood asthma. The objective of the study was to determine whether specific HLA class II genes (e.g., DRB1*03) are associated with asthma and whether such association explains the influences of family history of asthma or atopy on asthma incidence. A stratified random sample of 340 children who had HLA data available from the Rochester Family Measles Study cohort (n= 876) and a convenience sample of healthy children aged 5-12 years were the participants. We conducted comprehensive medical record reviews to determine asthma status of these children. The associations between the presence of specific HLA alleles and development of asthma and the role of family history of asthma or atopy in the association were evaluated by fitting Cox models. The cumulative incidence of asthma by 12 years of age among children who carry HLA DRB1*03 was 33%, compared to 24.2% among those who did not carry this allele. Adjusting for family history of asthma or atopy, gender, low birth weight, season of birth, HLA DRB1*04, and HLA DQB1*0302, the hazards ratio for HLA DRB1*03 carriers was 1.8 (95% confidence interval: 1.1-2.9, P= 0.020). We concluded that the HLA DRB1*03 allele is associated with asthma. However, the HLA class II gene does not explain the influences of family history of asthma or atopy on development of asthma. The mechanism underlying the association between asthma and HLA genes needs to be elucidated.
人类白细胞抗原(HLA) II类基因与哮喘或特应性家族史之间的关系尚不清楚。本研究的目的是确定特定的HLA II类基因(如DRB1*03)是否与哮喘相关,以及这种关联是否可以解释哮喘家族史或特应性对哮喘发病率的影响。从罗切斯特家庭麻疹研究队列(n= 876)中获得HLA数据的340名儿童和5-12岁健康儿童的分层随机样本作为参与者。我们进行了全面的医疗记录审查,以确定这些儿童的哮喘状况。通过拟合Cox模型评估特定HLA等位基因的存在与哮喘发展之间的关系,以及哮喘或特应性家族史在这种关系中的作用。携带HLA DRB1*03的12岁儿童哮喘的累积发病率为33%,而不携带该等位基因的儿童哮喘的累积发病率为24.2%。经哮喘或特应性家族史、性别、低出生体重、出生季节、HLA DRB1*04、HLA DQB1*0302等因素调整后,HLA DRB1*03携带者的危险比为1.8(95%可信区间:1.1 ~ 2.9,P= 0.020)。我们得出结论,HLA DRB1*03等位基因与哮喘有关。然而,HLAⅱ类基因并不能解释哮喘家族史或特应性对哮喘发生的影响。哮喘与HLA基因之间关联的机制有待阐明。
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引用次数: 36
Expression of APOBEC3G in kidney cells. APOBEC3G在肾细胞中的表达。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00725.x
Y Komohara, S Suekane, M Noguchi, K Matsuoka, A Yamada, K Itoh

The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), a member of the APOBEC family possessing DNA mutator activity through cytosine deamination, is reported to play an important role in host defense against infections such as those of hepatitis B virus and human immunodeficiency virus. Here, we examined the expression of APOBEC3G in human kidney cells to better understand its biological role against infection. APOBEC3G was immunohistochemically detectable in kidney mesangial cells and also to some extent in kidney epithelial tubular cells. In addition, overexpression of APOBEC3G was shown in renal carcinoma tissues and cell lines. APOBEC3G expression was upregulated by inflammatory cytokines, such as interferon, interleukin-6, and tumor necrosis factor. These results may provide new insight into the role of APOBEC3G in host defense against viral infection and cancer.

载脂蛋白B mrna编辑酶,催化多肽样3G (APOBEC3G)是APOBEC家族的一员,通过胞嘧啶脱胺具有DNA突变活性,据报道在宿主防御乙型肝炎病毒和人类免疫缺陷病毒等感染中发挥重要作用。在这里,我们检测了APOBEC3G在人肾细胞中的表达,以更好地了解其抗感染的生物学作用。肾系膜细胞和肾上皮小管细胞均可检测到APOBEC3G。此外,APOBEC3G在肾癌组织和细胞系中也有过表达。炎性细胞因子如干扰素、白细胞介素-6和肿瘤坏死因子上调APOBEC3G的表达。这些结果可能为APOBEC3G在宿主防御病毒感染和癌症中的作用提供新的见解。
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引用次数: 10
Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease. 人类MHC区域同时具有冠状动脉疾病的易感性和保护性单倍型。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00735.x
A Palikhe, J Sinisalo, M Seppänen, V Valtonen, M S Nieminen, M L Lokki

Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.

为了研究人类主要组织相容性复合体(MHC)区域在冠状动脉疾病(CAD)中的作用,我们招募了两个独立的患者材料和对照组。首先,心脏移植受者(n = 276)根据动脉粥样硬化的严重程度分为三个亚组。比较各组人白细胞抗原(HLA) a - b - dr单倍型及基因频率。其次,采用HLA-A、HLA-B、HLA-DRB1、LTA+253(a/g)、LTA+496(C/T)、LTA+633(C/ g)、LTA+724(C/ a)、C4A和C4B 9种MHC遗传标记对100例急性冠脉综合征(ACS)患者和74例健康对照进行MHC遗传标记评估,并比较其频率。在心脏移植受者中,HLA-DR1与CAD密切相关[严重vs无证据,优势比(OR) 2.37;95%置信区间(CI) 1.33-4.25;P = 0.003]。同样,在ACS患者中,HLA-DRB1*01与CAD相关(患者vs对照组,OR 2.36;95% ci 1.25-4.44;P = 0.007)。HLA-DRB1*01与低密度脂蛋白胆固醇相关(OR 5.32;95% ci 1.64-17.26;P = 0.005)和吸烟习惯(OR 3.13;95% ci 1.09-9.03;P = 0.035)为危险因素。最强的保护基因是HLA-B*07 (OR 0.46;95% ci 0.24-0.88;P = 0.02)或与单倍型LTA+253a-LTA+633g-C4A3-C4B1 (or 0.36;95% ci 0.22-0.57;P = 0.00001)。总之,人类MHC区域含有预防和易感CAD的基因。
{"title":"Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease.","authors":"A Palikhe,&nbsp;J Sinisalo,&nbsp;M Seppänen,&nbsp;V Valtonen,&nbsp;M S Nieminen,&nbsp;M L Lokki","doi":"10.1111/j.1399-0039.2006.00735.x","DOIUrl":"https://doi.org/10.1111/j.1399-0039.2006.00735.x","url":null,"abstract":"<p><p>Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.</p>","PeriodicalId":23105,"journal":{"name":"Tissue antigens","volume":"69 1","pages":"47-55"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-0039.2006.00735.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26480728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 36
Sequencing of a novel HLA-A allele, A*6836, showing a Bw4 epitope. 新的HLA-A等位基因a *6836的测序,显示一个Bw4表位。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00732.x
A Balas, F García-Sánchez, J L Vicario

A novel A*6836 allele was completely characterized by sequence-based typing (SBT) in a cord blood sample from an Ecuadorian donor. A*6836 discloses six clustered amino acid residue changes at the alpha-1 domain, codons 76-83, regarding its closer A*680102 allele. Therefore, A*6836 would be a new human leukocyte antigen (HLA)-A molecule showing a Bw4-epitope.

一种新的A*6836等位基因通过序列分型(SBT)在厄瓜多尔供体脐带血样本中被完全鉴定。A*6836在A*680102等位基因的α -1结构域密码子76 ~ 83处披露了6个簇状氨基酸残基变化。因此,A*6836可能是一个具有bw4表位的新的人白细胞抗原(HLA)-A分子。
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引用次数: 9
PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies. 胃癌组织中PD-L1表达分析及两种功能性单克隆抗体阻断肿瘤相关PD-L1信号传导
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00701.x
J Sun, K Xu, C Wu, Y Wang, Y Hu, Y Zhu, Y Chen, Q Shi, G Yu, X Zhang

Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.

程序性死亡-1配体-1 (Programmed death-1 ligand-1, PD-L1)是B7共刺激分子家族中的一员,在调节细胞和体液免疫应答中起重要作用。本研究成功制备了两种小鼠抗人PD-L1单克隆抗体10E10和2H11,并对其进行了进一步的表征。单克隆抗体10E10结合不同的PD-L1表位,比较了一系列恶性细胞系、活化的T淋巴细胞、B淋巴细胞和树突状细胞上可用的抗PD-L1单克隆抗体。然后用单克隆抗体2H11免疫组化染色,发现PD-L1在人胃癌标本中表达,而在正常组织和胃腺瘤组织中均未表达。另有数据显示,PD-L1是评价胃癌预后的决定性因素,抗人PD-L1单克隆抗体10E10可抑制肿瘤相关PD-L1诱导的t细胞凋亡。综上所述,我们制备的两种功能性小鼠抗人PD-L1单克隆抗体可能对进一步探索共刺激分子调控网络和肿瘤免疫治疗的免疫干预具有重要价值。
{"title":"PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies.","authors":"J Sun,&nbsp;K Xu,&nbsp;C Wu,&nbsp;Y Wang,&nbsp;Y Hu,&nbsp;Y Zhu,&nbsp;Y Chen,&nbsp;Q Shi,&nbsp;G Yu,&nbsp;X Zhang","doi":"10.1111/j.1399-0039.2006.00701.x","DOIUrl":"https://doi.org/10.1111/j.1399-0039.2006.00701.x","url":null,"abstract":"<p><p>Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.</p>","PeriodicalId":23105,"journal":{"name":"Tissue antigens","volume":"69 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-0039.2006.00701.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26480182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 70
HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population. 非裔美国人HLA-A, -B, -C, -DRB1等位基因和单倍型频率
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00728.x
B Tu, S J Mack, A Lazaro, A Lancaster, G Thomson, K Cao, M Chen, G Ling, R Hartzman, J Ng, C K Hurley

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.

基于序列的分型用于鉴定人类白细胞抗原(HLA)-A、-B、-C和-DRB1等位基因,这些等位基因来自564名非裔美国志愿者,他们被招募参加一个不相关的造血干细胞登记。HLA-A、HLA-B 67、HLA-C 33和HLA-DRB1 44个等位基因在每个位点上鉴定出的已知等位基因数为42个。鉴定了6个在初始序列特异性寡核苷酸探针检测中未发现的新等位基因(A*260104、A*7411、Cw*0813、Cw*1608、Cw*1704和DRB1*130502)。平衡选择的作用,塑造比预期更“均匀”的等位基因频率分布,被推断为所有四个基因座,特别是HLA-A和DRB1基因座。使用期望最大化算法估计2、3和4位点单倍型。与来自非洲和欧洲的其他人群的比较表明,尽管也注意到HLA-A:B单倍型频率与先前对非洲裔美国人个体的研究相似,但此处描述的非洲裔美国人人群中的欧洲人混合程度低于先前报道的其他非洲裔美国人人群。
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引用次数: 53
Kappa immunoglobulin light chain polymorphisms and survival after allogeneic transplantation for B-cell malignancies: a potential graft-vs-leukaemia target. b细胞恶性肿瘤异体移植后Kappa免疫球蛋白轻链多态性和存活:一个潜在的移植物抗白血病靶点。
Pub Date : 2007-01-01 DOI: 10.1111/j.1399-0039.2006.00729.x
T L Etto, L A Stewart, J Muirhead, M Bailey, A P Schwarer

In the human leucocyte antigen (HLA)-matched haematopoietic stem cell transplantation (HSCT) setting, minor histocompatibility antigen (mHA) disparities between recipient and donor can lead to graft-vs-host disease (GVHD) or graft rejection. Graft-vs-leukaemia (GVL) effect is a beneficial T-cell-mediated immune response that can also occur following HLA-matched HSCT. mHAs with tissue expression restricted to cells of the haematopoietic system are particularly relevant as immunotherapeutic targets for destroying malignant cells without inducing GVHD. Therefore, it is important to identify further haematopoietic-restricted polymorphic mHAs, which may have the potential to be used clinically for adoptive immunotherapy. Polymorphic mismatching of minor antigens, such as the B-cell-specific protein, the kappa immunoglobulin light chain (kappa) may play a role in the incidence of GVL and therefore the survival of transplant recipients following transplantation for B-cell malignancies. Polymorphisms in the constant region of the immunoglobulin kappa polypeptide chain have been defined involving single amino acid changes at positions 153 and 191. In this study, 51 HLA-matched B-cell malignancy transplant pairs were kappa typed by polymerase chain reaction and restriction enzyme digestion to investigate the association between kappa allotype disparity and outcome after transplantation. Kappa allotype disparity between transplant pairs may be associated with an increased survival compared with pairs not mismatched for kappa, as kappa mismatched recipients had a higher percentage of complete remissions and a decreased level of relapse in comparison with the nonmismatched recipients. HLA peptide prediction software was used to determine which HLA types were the best binders for kappa peptides. It was observed that patients with tissue types predicted to bind the kappa Km(1,2) peptides had better survival outcomes and no relapse compared with those with tissue types not predicted to bind the kappa Km(1,2) peptides. This study may contribute to the assessment of the clinical role of kappa with regard to the outcome of allogeneic transplantation for B-cell malignancies.

在人白细胞抗原(HLA)匹配的造血干细胞移植(HSCT)环境中,受体和供体之间微小的组织相容性抗原(mHA)差异可导致移植物抗宿主病(GVHD)或移植物排斥反应。移植物抗白血病(GVL)效应是一种有益的t细胞介导的免疫反应,也可以在hla匹配的HSCT后发生。组织表达局限于造血系统细胞的mHAs作为破坏恶性细胞而不诱导GVHD的免疫治疗靶点尤其相关。因此,进一步鉴定造血限制性多态mHAs是很重要的,这可能有潜力在临床上用于过继免疫治疗。次要抗原的多态性错配,如b细胞特异性蛋白,kappa免疫球蛋白轻链(kappa)可能在GVL的发生率中发挥作用,从而影响b细胞恶性肿瘤移植后移植受体的生存。免疫球蛋白kappa多肽链恒定区域的多态性已被确定,涉及153和191位单氨基酸的变化。本研究通过聚合酶链反应和限制性内切酶酶切对51对hla匹配的b细胞恶性移植对进行kappa分型,探讨kappa异型差异与移植后预后的关系。与Kappa不匹配的受体相比,移植对之间的Kappa同种异型差异可能与Kappa不匹配的受体的生存率增加有关,因为Kappa不匹配的受体与未匹配的受体相比具有更高的完全缓解百分比和更低的复发水平。HLA肽预测软件用于确定哪种HLA类型是kappa肽的最佳结合物。我们观察到,与那些不结合kappa Km(1,2)肽的组织类型相比,预测结合kappa Km(1,2)肽的组织类型的患者有更好的生存结果,没有复发。这项研究可能有助于评估kappa在b细胞恶性肿瘤同种异体移植预后方面的临床作用。
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引用次数: 1
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Tissue antigens
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