矽肺与人类白细胞抗原-DRB1·和-DQB1·基因相关性的研究

目的 探讨我国北方汉族人矽肺的易感性与人类白细胞抗原（HLA）－DRB1＊、DQB1＊位点等位基因多态的相关性。方法 用序列特异性引物的聚合酶链式反应（PCR－SSP）方法，分析48名汉族矽肺患者及100名汉族无血缘关系对照者（均为有过14年以上接尘史的井下凿岩工）HLA－DRB1＊、DQB1＊位点的基因频率分布，以相对危险度（RR）代表相关程度。结果 在矽肺患者组中，DRB1＊1401、DQB1＊05的等位基因频率明显高于对照组，经统计学处理，两组间差异具有显著性（χ^2=5.61,P=0.0066,RR=17.40;χ^2=10.70,P=0.0011,RR=3.81)；而DRB1＊09的等位基因频率则明显低于对照组，差异有显著性（χ^2=5.70,P=0.0187,RR=0.21)；其他等位基因频率的分布差异无显著性（P＞0．05）。结论 HLA－DRB1＊1401、DQB1＊05可能与矽肺的易感性有关，而DRB1＊09则可能与机体抗矽肺的保护性有关。HLA－DR位点与机体易感及保护的双重作用有关，等位基因之间的共同作用可能是影响矽肺发生的原因之一。     

Detection of anti-topoisomerase I autoantibody in patients with silicosis

Objectives The aim of this study was to detect anti-topoisomerase I (anti-topo I) autoantibodies, which are known to be limited in systemic sclerosis patients, in silicosis patients with no clinical symptoms of autoimmune disease. Methods Serum anti-topo I autoantibodies were detected using ELISA. Differences in clinical parameters between patients with and without anti-topo I autoantibodies were analyzed. Results Seven of 69 patients had anti-topo I autoantibodies. These 7 patients showed elevated PaCO₂ values (P=0.0212), and inverse correlations between serum soluble Fas levels and PaCO₂ values were found. Conclusion Anti-topo I autoantibodies were detected in 10.1% of silicosis patients without any clinical symptoms of autoimmune disease. The findings here suggest that the genesis of anti-topo I autoantibodies might be related to pulmonary involvement or lung fibrosis associated with progression of silicosis.     

HLA-DRB1、DQB1基因多态性与肾综合征出血热相关性研究

目的探讨HLA-DRB1、DQB1基因多态性与肾综合征出血热(HFRS)相关性。方法选取2007—2016年辽宁省铁岭市辖区内医院收治的HFRS患者300例为研究组研究对象,另选取300名健康体检者为对照组研究对象;利用序列特异性引物–聚合酶链反应(PCR-SSP)技术检测2组的HLA-DRB1、HLA-DQB1基因分型,分别比较2组HLA-DRB1、HLA-DQB1基因频率(GF),并计算相对危险率(RR),采用Pearson线性相关分析HLADRB1、DQB1基因多态性与HFRS相关性。结果研究组患者HLA-DRB1等位基因共可检测出12个基因位点,对照组HLA-DRB1等位基因共可检测出13个基因位点,且研究组HLA-DRB1*16 GF为8.0%,明显高于对照组GF的1.0%(RR=6.60,χ2=4.39,P<0.05);2组其余HLA-DRB1等位基因GF差异无统计学意义(P>0.05);研究组DQB1各等位基因与对照组相比差异无统计学意义(P>0.05);Pearson线性相关分析结果显示,HLA-DRB1*16基因与流行性出血热呈正相关关系(OR=2.014,95%CI=0.373~10.132,P<0.05),DRB1*10基因与HFRS呈正相关关系(OR=2.273,95%CI=0.254~9.252,P<0.05)。结论 HLA-DRB1*16、HLA-DRB1*16基因与HFRS呈正相关关系,HLA-DRB1*16、HLA-DRB1*10基因可能是HFRS易感基因之一,可能是HFRS发生中的危险因素。     

人类白细胞抗原DRB1*和DQB1*基因多态性与尘肺发病的相关性

目的探讨人类白细胞抗原（HIA）DRB1＊和DQB1＊位点基因多态性与尘肺发病的关系。方法采用1：1配比的病例一对照研究方法。尘肺病例组为113名Ⅰ期尘肺患者，对照组为与尘肺病例组年龄相近、同性别、同民族、同一工作地点、开始接尘时间和累积接尘工龄相差不超过2年的接尘工人。用聚合酶链反应序列特异性引物分析方法检测HIA-DRB1＊和DQB1＊共9个位点的等位基因。用SAS6．12软件进行单因素和多因素分析。结果尘肺病例组的HIA—DRB1＊08等位基因频率高于对照组，差异有统计学意义（P〈0.01），OR值为6．000，95％CI：1．906～18．941：HIA—DRB1＊09、HLA—DQB1＊06等位基因频率低于对照组，差异有统计学意义（P〈0．01），OR值为0．259、0．300，95％CI为：0．115～0．584、0．144～0．627；1：1条件logistic回归分析表明，HIA-DRB1＊08、HIA—DRB1＊09和HIA—DQB1＊06等位基因频率与尘肺有关联，调整OR值分别为：7．804、0．225和0．269，95％CI分别为：2．077—29．307、0．083—0．609和0．117～0．613。生存分析表明，HIA—DRB1＊08等位基因为尘肺潜伏期的危险因素；HIA—DQB1＊06为保护因素。结论HIA—DRB1＊08等位基因可能为尘肺易感的危险因素，HLA—DQB1＊06可能是抗尘肺的保护性的等位基因。     

HLA-DRB1和DQB1基因多态性与药物肝损害关联研究的meta分析

目的对人类细胞抗原（human leukocyte antigen system,HLA）基因多态性和药物性肝损害的关联性研究现状进行系统综述,并用meta分析的方法总结可能的诱发药物性肝损害的HLA基因多态性位点。方法主题词检索PubMed和EmBase电子数据库,根据预先设定的纳入排除标准对文献进行评价,对符合纳入标准的文献进行信息提取。对HLA-DRB1*15、*07、*03和HLA-DQB1*06、*02进行meta分析并计算合并OR值。结果纳入11篇文献共14个研究报道HLA基因多态性与药物性肝损害的关联。根据meta分析结果,药物性肝损害病例组与对照组相比,具有更高的HLA-DRB1*15、DQB1*06基因型比例（OR=2.82,95%CI:1.31～6.07,P<0.001;OR=3.47,95%CI:1.77～6.81,P<0.001）。结论 HLA-DRB1*15和HLA-DQB1*06基因型可能是药物性肝损害发生中的危险因素。     

上海市汉族人群乙型肝炎疫苗免疫应答与HLA-DRB1等位基因的关系

目的 探讨上海市汉族人群对乙肝疫苗（hepatitis B vaccine,HepB）免疫应答与人类白细胞抗原（human leukocyte antigen,HLA）-DRB1等位基因的关系。方法 600名上海市汉族人群检测五项HBV血清学标志物,对其中全为阴性的237人以常规程序接种HepB后,采用聚合酶链反应序列特异性引物（polymerase chain reaction sequence specific primers,PCR-SSP）分型技术,对32例接种HepB后呈低、无应答者及54例正常应答者的等位基因进行HLA-DRB1检测。结果 两组观察对象性别、年龄差异均无统计学意义（均有P>0.05）。低、无应答组HLA-DRB1*07的频率（16.67%）高于正常组（0.00%）、HLA-DRB1*09的基因频率（37.50%）高于正常应答组（5.56%）,差异均有统计学意义（均有P<0.05）;HLA-DRB1*04的频率（3.13%）低于正常应答组（20.37%）,差异有统计学意义（P=0.022）。而其他HLA-DRB1基因的频率差别均无统计学意义。结论 上海汉族人群HepB低、无应答与HLA-DRB1有关,HLA-DRB1*04、DRB1*07、DRB1*09可能为低、无应答的易感基因。     

8-Hydroxydeoxyguanosine in leukocyte DNA and urine of quartz-exposed workers and patients with silicosis

Objective: To examine radical-induced DNA damage and its elimination in workers exposed to quartz and in patients with silicosis, and to assess the relationship of these effects to lung function. Methods: Blood and spontaneous urine samples were obtained from active, quartz-exposed workers without silicosis (n=63), and from retired workers with silicosis (n=42). Levels of 8-hydroxydeoxyguanosine (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use of high-performance liquid chromatography coupled with ultra violet- (UV) and electrochemical detection. Results: No significant differences in the mean levels of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between silicosis patients and quartz-exposed healthy workers. However, in the group of silicosis patients with increased oxidative DNA damage the urinary excretion of 8-OHdG was lower than in the corresponding group of active workers without silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8-OHdG in DNA correlated negatively, with forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC). Healthy workers with a personally estimated high dust exposure in the workplace showed higher levels of 8-OHdG in DNA than did workers with moderate dust exposure. No association of 8-OHdG formation and/or elimination with duration of employment, field of activity, smoking or age was found. Conclusion: Our findings suggest that a less effective repair of 8-OHdG is associated with a higher degree of pulmonary airway obstruction in patients with silicosis. Received: 13 August 1999 / Accepted: 5 January 2000     

中国南方人DQB1、DRB1等位基因与妊娠期高血压疾病的关系

目的:探讨DQB1及DRB1座位等位基因与妊娠期高血压疾病的关系,阐明妊娠期高血压疾病发生发展的免疫机制。方法:采用快速离心柱法提取对象外周血白细胞DNA,以荧光分光光度计测定DNA含量,应用顺序特异性引物聚合酶链反应技术(PCR-SSP)进行基因测定;取20例妊娠期高血压疾病者作为研究组,18例正常孕妇作为对照组。结果:从单一基因分析,研究组频率显著增高的基因有:DRB1*0303、DRB1*0405、DRB1*0403、DRB1*06011/12、DQB1*0502、DOB1*0402,其中DRB1*0405、DQB1*0502风险处于最高值(RR值分别为9.76、6.34),基因频率显著高于对照组(P<0.05),频率显著降低的基因是:DRB1*0407、DRB1*0315、DQB1*03011/12、DQB1*05031,基因频率显著低于对照组(P<0.05)。2个PIH相关基因组成1个单倍型,其中DRB1*0315-DQB1*0502、DRB1*0405-DOB1*06012单倍型与妊娠期高血压疾病患者尿蛋白及血压呈正相关关系(Pc<0.05)。结论:DRB1和DQB1两座位上等位基因与妊娠期高血压疾病发生密切相关。     

矽肺和矽肺结核患者体内Th1/Th2类细胞因子的研究

目的 探讨矽肺和矽肺结核患者体内是否存在Th1/Th2失衡.方法 选择69名矽肺和矽肺结核患者作为研究对象,另以24名健康人为对照,使用酶联免疫吸附试验对血清白细胞介素(IL)4、IL-10以及肿瘤坏死因子-αTNF-α)进行检测和统计分析.结果 矽肺和矽肺结核组血清TNF-α低于对照组,而血清IL-10和IL-4明显高于健康对照组.矽肺、矽肺结核组IL-4、IL-10以及TNF-α与健康对照组比较差异有显著性(P<0.05或P<0.01).结论 矽肺和矽肺结核患者机体细胞免疫功能低下,存在Th1反应减弱,Th2反应增强.     

Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among community-based Caucasian females with rheumatoid arthritis

Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70–74 are associated with susceptibility to rheumatoid arthritis (RA). However, the nature of the association and the mode of inheritance differ depending upon the source of RA patients and laboratory methodology. We studied the relative predispositional effects (RPE) and mode of inheritance of DRB1 alleles among a community-based sample of 180 RA patients and 116 healthy controls, all Caucasian females. Polymerase chain reaction (PCR)-based assays were used for DRB1 genotyping, and the genotypic distributions were analyzed by both the RPE and antigen genotype frequency among patients (AGFAP) methods. We examined the evidence of synergy among DRB1 alleles for RA risk by comparing the observed DRB1 genotype distribution to that predicted under Hardy-Weinberg equilibrium. Fifty-six percent of RA cases were attributable to DRB1 alleles encoding the SE. The RPEs of DRB1 alleles were *0401 > *0404 > *1001 > *0408 > *0101. The strength of the RA association was not significantly different for these alleles. The AGFAP analysis was consistent with a recessive mode of inheritance for DRB1 alleles, while an additive (dominant) model was rejected. We found no evidence of synergy for RA risk among individual DRB1 alleles based on comparison of the observed vs. Predicted genotype distributions. These results suggest that among community-based Caucasian females with RA, the DRB1 RA susceptibility gene influences disease risk in a recessive fashion without synergy among individual DRB1 alleles. Genet. Epidemiol. 15:123–134,1998. © 1998 Wiley-Liss, Inc.     

矽肺及矽肺结核患者血液黏度和体外血栓的研究

目的：探讨矽肺以及矽肺结核患者血液黏度和体外血栓的变化。方法：检测288例矽肺患者、178例矽肺结核患者以及150例健康对照者血液黏度和体外血栓的长度和干重。结果：矽肺组和矽肺结核组与正常对照组比较血液黏度（Ⅰ期矽肺除外）和体外血栓均显著增高,患者各组内Ⅰ、Ⅱ及Ⅲ期间血液黏度亦随期别增加而递增,且差异显著,体外血栓无显著差异;Ⅰ、Ⅱ期矽肺结核患者分别与同期矽肺患者比较,全血黏度在高、中剪切率下显著增加,在低剪切率下以及血浆黏度差异无显著性,体外血栓长度和干重亦增加显著;Ⅲ期矽肺结核患者与Ⅲ期矽肺患者比较,血液黏度和体外血栓均无显著差异。结论：矽肺患者血液呈高黏、高凝状态,且随期别增加血液黏度和体外血栓长度及干重均相应增加,合并结核者尤甚。     

Symptoms and clinical findings in patients with silicosis

Respiratory symptoms, radiographic findings, and lung function were analyzed in 144 Finnish patients with silicosis. The prevalence of persistent phlegm production in these patients was 46% and that of dyspnea 87%. Impairment of the vital capacity (VC) and the diffusion capacity (DLCO) (less than 80% of predicted values) were found in 46 and 47% of the patients with simple silicosis, respectively. The mean DLCO was lower in patients with advanced simple silicosis (category 3) than in those with slight simple silicosis (categories 1 and 2). In category 3 the DLCO was impaired in 9 out of 12 patients, the impairment being below 65% of the predicted values in six of the nine. All patients with large opacities showed impairment in their lung function tests. Twenty-eight of the silicosis patients had referents matched for exposure to silica dust, age, and gender. The referents had no radiographic signs of silicosis. The patients experienced dyspnea more often than their referents, whereas no difference was found in the prevalence of persistent phlegm production. The mean values of VC, forced expiratory volume in 1 s (FEV1.0), and DLCO were lower in the patients than in the referents. The results indicate a high prevalence of dyspnea, restrictive impairment of lung function, and impaired diffusion capacity in the patients with simple or complicated (ie, large radiographic opacities) silicosis. The DLCO proved to be a rather sensitive lung function parameter for advanced simple silicosis.     

矽肺患者血浆内皮素－1含量变化

为探讨内皮素－１（ＥＴ－１）在矽肺发病中的意义，对３６例矽肺患者、２０例矽尘作业工人和３０例未接触矽尘的健康人分别进行肺功能、动脉血气和动脉血浆ＥＴ－１含量测定。结果表明矽肺患者血浆ＥＴ－１显著高于其它二组；Ⅲ期矽肺显著高于Ⅱ期，Ⅱ期矽肺显著高于Ⅰ期；矽肺血浆ＥＴ－１含量与矽尘作业工龄呈显著正相关；Ⅲ期矽肺ＥＴ－１含量分别与ＦＶＣ、ＦＥＶ＿１％、ＰａＯ＿２呈显著负相关。上述结果说明矽肺血浆ＥＴ－１含量不但明显升高，而且与病情相关，因此ＥＴ－１可能与矽肺的发病过程有关。     

可溶性细胞间黏附分子-1在矽肺患者血清中的表达

应用酶联免疫吸附试验分别检测100例非矽肺接尘工人,54例Ⅰ期矽肺患者血清中可溶性细胞间黏附分子-1(sICAM-1)的含量.经成组设计:检验,两组研究对象在年龄及接尘工龄上,差异无统计学意义(P>0.05),sICAM-1的含量在Ⅰ期矽肺患者血清中显著高于非矽肺接尘工人(P<0.05).提示sICAM-1可能是参与矽肺发生发展的重要免疫指标,且在矽肺形成早期即呈现高表达.     

Cytokine-driven inflammatory response is associated with the hypermetabolism of AIDS patients with opportunistic infections

BACKGROUND: To assess a possible role of systemic inflammation in the resting metabolic response in AIDS patients with active secondary infections. METHODS: Fifty-two patients with AIDS-defined criteria and concomitant active infections and 19 healthy subjects were studied. Measurements were as follows: body composition assessed by bioelectrical impedance; resting energy expenditure (REE) by 30-minute indirect calorimetry; cytokine concentrations (IL-6, IFNalpha, TNFalpha, sTNF-R1) by ELISA; C-reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, and nutritional parameters by standard techniques. RESULTS: REE adjusted for fat-free mass (REEFFM) was significantly increased in AIDS patients despite 39% of them not being hypermetabolic. The patients were undernourished and were found to have increased levels of acute-phase proteins and increased concentrations of IL-6 and sTNF-R1 relative to controls. REE parameters were positively related to CRP, ESR, ferritin, IL-6, and sTNF-R1 and negatively related to albumin, prealbumin, and transferrin. CRP was an independent predictor of REEFFM in AIDS patients and explained 25% of its variability. Patients with severe inflammation (CRP > or = 37 mg/dL) were significantly hypermetabolic with respect to patients without inflammation (CRP < 6 mg/dL) and had higher levels of IL-6 and sTNF-R1 and lower levels of albumin and prealbumin. Although no significant differences were observed with respect to the infection type, patients with tuberculosis and Pneumocystis carinii infections had higher resting metabolic and inflammatory responses, whereas patients with recurrent bacterial pneumonia were normometabolic and had lower levels of inflammatory markers. CONCLUSIONS: Resting hypermetabolism observed in AIDS patients with concurrent active infections is related to the presence and severity of systemic cytokine-driven inflammatory response, which could reflect the type of secondary infection.     

100例Ⅰ期矽肺患者血气分析

对１００例Ⅰ期矽肺进行了血气分析,结果表明ＰＯ２是一项敏感指标,１００例中５３例低于１０．７ｋＰａ,导致ＰＯ２降低的原因主要是小气道损害、分流量及生理死腔增加。     

HLA-DRB1* and DQB1* allele and haplotype diversity in eight tribal populations: Global affinities and genetic basis of diseases in South India

The distribution of HLA class-II DRB1* and DQB1* alleles/ haplotypes were studied in 438 individuals of 8 Dravidian tribal groups inhabiting the Western Ghats, south India. The HLA typing was performed by PCR-SSP method. In order to identify the 5-locus Ancestral Extended Haplotypes (AEH), the alleles of HLA-A, -B and -C loci were typed for DNAs with predominant 2-locus haplotypes. The analyses have revealed allele HLA-DRB1*15 as the most predominant allele (Lowest / Highest range: Urali, 14.81 / Malasar, 48.94), followed by the alleles DRB1*10 (Katunayakan, 1.85 / Paliyan, 48.21), DRB1*14 (Paliyan 4.46 / Katunayakan, 40.74), DRB1*12 (Mannan, 1.64 / Katunayakan, 20.37) and DRB1*03 (Mannan, 1.64 / Urali, 29.63). The most frequent DQB1* alleles were DQB1*02 (Paliyan 3.57 / Urali, 23.15), DQB1*05 (Katunayakan, 27.77 / Paliyan 84.82) and DQB1*06 (Malasar, 8.51 / Kuruman, 33.51). The most predominant two-locus haplotypes observed were DRB1*15-DQB1*05, DRB1*10-DQB1*05, DRB1*15-DQB1*06 and DRB1*04-DQB1*05. The present study of HLA immunogenetics of south Indian tribes have revealed the presence of globally shared two and 5-locus haplotypes. Many of these haplotypes were implicated in a number of diseases in south India. We observed the presence of ancestral extended haplotypes (AEHs), hitherto not reported in Indian populations such as, A*68-B*35-C*02-DRB1*15:01-DQB1*05:01, A*24-B*57-C*06-DRB1*04:01-DQB1*05:01 and A*24-B*35-C*02-DRB1*15:01-DQB1*05:02. The dendrogram based phylogenetic analyses have revealed the Caucasian affinity of Urali, palaeo-Mediterranean and Indo-European affinity of Malasar tribes. The presence of globally shared susceptible and protective haplotypes reiterated the mosaic immunogenetic fabric of south Indian tribes.