中国人群1型糖尿病HLA-DQ基因多态性的Meta分析

目的　综合评价中国人群HLA DQ基因多态性与 1型糖尿病 (DM)的关联性。方法　以 1型DM组和健康对照组的各HLA DQ等位基因频数(基因型频数、单倍型频数 )分布的OR值为统计量,全面检索相关文献;应用Meta分析软件包REVMAN4. 2,在基因分型水平上,对各研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果　等位基因DQA1* 0301、DQA1* 0501、DQB1* 0201、DQB1* 0303、DQB1* 0401和DQB1* 0604是中国人群 1型DM的危险基因 (均P<0. 05), 他们的合并OR值分别为2. 83、2. 90、4. 17、1. 65、2. 00和 3. 00;基因型 (或单倍型 )DQA1* 0301 /DQB1* 0201、DQA1* 0301 /DQB1*0302、DQA1* 0501 /DQB1* 0201、DQA1* 0301 /DQB1* 0201 /DRB1* 0301和DQB1* 0302 /DRB1* 0405是中国人群 1型DM的危险基因型(或单倍型,均P<0. 05),他们的合并OR值分别为 8. 95、3. 09、6. 01、6. 57和 14. 85。而等位基因DQA1* 0101、DQA1* 0102、DQA1* 0103、DQA1* 0104、DQA1* 0201、DQA1* 0401、DQA1* 0601、DQB1* 0301、DQB1* 0501、DQB1* 0503、DQB1* 0601和DQB1* 0602是中国人群 1型DM的保护等位基因(均P<0. 05),他们的合并OR值分别为 0. 47、0. 38、0. 21、0. 07、0. 44、0. 39、0. 44、0. 19、0. 33、0. 32、0. 42和 0. 28; 基因型     

类风湿关节炎HLA-DQβ1易感基因研究

目的 探讨HLA-DQβl基因多态性在中国汉族类风湿关节炎(RA)发病中的作用及与患者临床指标的关系。方法 选取类风湿关节炎患者及健康对照各42例，以序列特异性引物PCR(PCR—SP)技术对HLA-DQβl的42种亚型进行检测，并分析患者病情、免疫学指标及关节破坏程度与各亚型之间的关系。结果 在RA患者组中HLA-DQβl*0401和*0501等位基因的频率(分别为11．9％、7．1％)显著高于对照组(分别为3．6％、1．2％)(X^2＝4．085，RR＝4．06；X^2＝4．725，RR＝6．83;P＜0．05)，而HAL-DQβ1*0602的频率则明显低于对照组(7．1％vs19．0％)(x^2＝5．23 ;P＜0．05)。HLA-DQβ*l0401／0301或*0401/0303及HLA-DQβl*0501/0301基因型在RA患者中的阳性率(分别为19．05％、9．52％)显著高于对照组(分别为2．38％、0％＞(X^2＝6．098，P＝0．014；X^2＝4．200，P＝0．040)，差异具有显著性。HLA-DQβl*03阳性的RA患者与阴性患者相比发病年龄早，关节破坏严重，关节外表现明显增多，并与部分实验室指标异常呈正相关，其中HLA-DQβ1*03纯合子(HLA-DQβl*03/03)患者的上述异常更为显著。结论 HLA-DQβl*0401及*0501亚型、HLA-DQβl*0401／03及HLA-DQβ1l*0501用301基因型可能与中国汉族RA的易感性有关，而HLA-DQβl*0602可能为抗RA基因;HLA-DQβl*03则与RA的严重程度相关。     

1型糖尿病与HLA-DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患者及23例正常对照的HLA-DQB1等位基因.用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)及胰岛素自身抗体(IAA).结果在1型患者中,DQB1*0201、*0303、*0604等位基因频率显著高于对照(P＜0.05),DQB1*0301则低于对照(P＜0.05),其余DQB1等无显著性差异.等位基因为DQB1*0201的患者中GADA阳性率显著高于阴性率.结论在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因.DQB1*0201可能对GADA的产生起允许作用.     

中国大陆汉族人群类风湿关节炎与HLA-DRB1*0401基因的相关性分析

目的 探讨中国大陆汉族人群类风湿关节炎(RA)与人类白细胞抗原(HLA)-DRB1*0401基因的关联情况。方法 检索已发表的有关中国大陆汉族人群RA患者和HLA-DRB1*0401的文献，进行Meta分析。结果 国内7项研究共578例RA患者和743例正常对照，DRB1*0401基因亚型是中国大陆汉族人群RA的关联基因(OR=2．66，P=0．004)。结论 Meta分析证实DRB1*0401与中国大陆汉族人群RA有相关性，样本大小对基因关联分析有重要影响。     

中国HLA-DQ基因多态性与重症肌无力相关性的系统评价

目的运用循证医学系统评价我国人类白细胞抗原(HLA)-DQ基因多态性与重症肌无力(MG)之间的相关性。方法计算机检索Pubmed、Ovid、Embase、CBM、CNKI、万方数据库、VIP等,查找2016年6月前发表的关于我国HLA-DQ基因多态性与MG之间关联的文献。按Cochrane系统评价的方法,由两名研究者独立进行质量评价和资料提取,采用RevMan5.2软件进行Meta分析。结果共纳入15篇文献,样本量为2 364例,其中病例组(MG组)1 073例,健康对照组1 291例。Meta分析结果示:增加重症肌无力风险的HLA-DQ等位基因有:HLA-DQA1*0102[OR=1.43,95%CI(1.14,1.81)]、HLA-DQB1*0301[OR=1.62,95%CI(1.29,2.03)]、HLA-DQB1*0501[OR=1.53,95%CI(1.16,2.01)];降低重症肌无力风险的HLA-DQ等位基因有:HLA-DQA1*0201[OR=0.61,95%CI(0.45,0.83)]、HLA-DQB1*0601[OR=0.55,95%CI(0.44,0.69)]、HLA-DQB1*0602[OR=0.49,95%CI(0.38,0.62)]。结论中国人群,重症肌无力的易感基因HLA-DQA1*0102、HLA-DQB1*0301、HLA-DQB1*0501,而HLA-DQA1*0201、HLA-DQB1*0601、HLA-DQB1*0602为重症肌无力的保护基因。     

肠易激综合征与HLA-DQB1基因多态性的相关性研究

目的 研究HLA-DQB1等位基因多态性与我国广东籍汉族肠易激综合征(IBS)遗传易感的相关性.方法 应用PCR及基因测序技术分析广东籍汉族IBS患者60例和健康对照者DQB1的基因分型,比较基因位点的发生频率的分布差异.结果 与正常对照组相比,IBS患者DQB1* 02等位基因的频率较低,DQB1*0603的频率较高,DQB1* 0601、DQB1* 0602、DQB1* 0604的频率与正常对照组相比无显著性差异,IBS各临床亚型之间等位基因的频率无明显差异.结论 DQBl* 02或DQB1* 0603等位基因可能是我国广东籍汉族人群IBS的易感基因.HLA-DQ基因多态性与IBS的临床分型无关.     

1型糖尿病与HLA—DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患及23例正常对照的HLA-DQB1等位基因。用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体（GADA）、胰岛细胞抗体（ICA）及胰岛自身抗体（IAA）。结果在1型患中,DQB1*0201、*0303、*0604等位基因频率显高于对照（P＜0.05),DQB1*0301则低于对照（P＜0.05),其余DQB1等无显性差异。等位基因为DQB1*0201的患中GADA阳性率显高于阴性率。结论：在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因。DQB1*0201可能对GADA的产生起允许作用。     

中国内地人群类风湿关节炎与HLA-DRB1共同表位基因关联性的Meta分析

目的探讨中国内地人群类风湿关节炎(RA)与人类白细胞抗原(HLA)-DRB1共同表位(SE)基因的关联情况。方法检索已发表的有关中国内地人群RA和HLA-DRB1的文献,进行汇总分析分析。结果14项研究共纳入1118例RA患者和1301名正常对照,中国内地人群RA的关联基因有HLA-DR4[比值比(OR)=4.05,P<0.0001)]、DRB1*0401(OR=2.66,P=0.004)、DRB1*0404(OR=2.10,P=0.02)、DRB1*0405(OR=3.98,P<0.0001)、DRB1*0410(OR=3.36,P=0.008)、SE(OR=2.75,P<0.00001)。其中DRB1*0405是主要基因亚型。结论汇总分析分析不仅证实了DRB1*0405与中国内地人群RA的关联,而且发现了相对少见基因亚型DRB1*0401、DRB1*0404、DRB1*0410与RA的关联,样本大小对基因关联分析的结论有重要影响。     

DQB1等位基因多态性与乙肝后肝硬化的遗传易感性研究

目的研究HLA-DQB1等位基因多态性与肝硬化的遗传易感性,为寻找肝硬化的易感基因或抗病基因提供线索.方法应用PCR-SSP技术检测106例湖北汉人乙肝后肝硬化患者和108例正常人HLA-DQB1等位基因,并结合临床资料进行比较分析.结果肝硬化组DQB1*0501等位基因频率明显升高(24.52%vs 11.11%,RR=2.6,P＜0.01),DQB1*0602等位基因频率明显下降(4.7%vs 12.03%,RR=0.3618,P＜0.05),其他等位基因频率在两组之间无显著性差异.提示DQB1*0501等位基因与湖北地区汉人乙肝后肝硬化关联,DQB1*0602等位基因则呈负关联.结论DQB1*0501等位基因可能是湖北地区汉族人乙肝后肝硬化的易感基因,DQB1*0602则为抵抗基因.     

1型糖尿病一级亲属胰岛自身抗体与HLA-DQ基因型的关系

目的探讨1型糖尿病一级亲属谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）与HLA—DQ基因型之间的关系。方法横断面、病例对照研究。采用放射配体法检测351例糖耐量正常的1型糖尿病一级亲属与376名正常对照者GADA、IA-2A与IAA。其中156例自身免疫1型糖尿病一级亲属与278名正常对照采用PCR-直接测序法明确HLA-DQ基因型。结果（1）与正常对照比较，1型糖尿病一级亲属DQA1＊03、DQB1＊0303、＊0401等位基因与DQA1＊03-DQBl＊0303、DQA1＊05-DQB1＊0201、DQA1＊03-DQB1＊0401单体型频率增高（均P〈0．05或P〈0．01），而DQA1＊0601、＊0201和DQB1＊0301、＊0602等位基因与DQA1＊0102-DQB1＊0602单体型频率减少（均P〈0．05或P〈0．01）。（2）与1型糖尿病患者比较，1型糖尿病一级亲属DQA1＊03等位基因频率减少（45．8％vs54．5％，P〈0．05）。（3）携带DQA1＊03-DQB1＊0303单体型者，GADA、IA-2A与IAA任一自身抗体阳性率高于不携带此单体型者（23．0％们8．6％，P〈0．05）。结论携带DQA1＊03-DQB1＊0303单体型的一级亲属，GADA、IA-2A与IAA任一自身抗体检出率最高。     

Analysis of cytoplasmic and surface antigens in childhood T-cell acute lymphoblastic leukaemias: clinical relevance of cytoplasmic TCRβ chain expression

SUMMARY. Expression of surface and cytoplasmic antigens on the blasts from 42 cases of childhood T-cell acute lymphoblastic leukaemia (T-ALL) were analysed. All with childhood T-ALL, except for one case expressing cytoplasmic TCR δ chain, were classified on the basis of differential expression of cytoplasmic CD3 (cCD3), TCRβ chain (cTCR β) and surface CD3 (sCD3) into the following three groups: group I (cCD3+, cTCRβ-, sCD3-), eight cases (19.5%); group II (cCD3+, cTCRβ+, sCD3-), 23 cases (56.1%); group III (cCD3+, cTCRβ+, sCD3+), 10 cases (24.4%). Each group defines the stepwise maturational stage of the CD3/TCR complex along the intrathymic T-cell differentiation. Group I had the lowest initial WBC count among the three groups ( P < 0.05) and showed significantly ( P < 0.05) a higher event-free survival (0.75) than those of group II (0.33). There was no significant difference in both the initial WBC count and the event-free survival between groups II and III. Thus, the absence of cTCRβ in sCD3-negative T-ALL appears to be a good prognostic factor, suggesting that this classification provides a useful tool to predict the prognosis of childhood T-ALL. This is the first report, to our knowledge, studying the relationship between the expression of cytoplasmic CD3/TCR antigens and the clinical features in T-ALL.     

Ultrastructural localization of major hydatid fluid antigens in brood capsules and protoscoleces of Echinococcus granulosus of human origin

Monospecific rabbit antisera obtained through experimental immunization with previously purified proteins were used in the ultrastructural localization of two hydatid fluid antigens, in brood capsules and protoscoleces of Echinococcus granulosus of human origin. The antigen-antibody reaction was revealed by a colloidal gold based method. Reaction was evident in the connective region of the germinal membrane and in the parenchyma of the protoscoleces. Both antigen 5 and antigen B were located in the interstitial material between the parenchymal cells and precisely associated with disorganized areas. The brood capsule wall and the brood capsule contents, the tegument of the protoscoleces, the parenchymal cells, the muscle cells, the calcareous corpuscles and the hooks did not contain antigen 5 or antigen B. Label was not observed in the lumen of the collecting ducts or in the flame cells, although antigen 5 was evident in the periluminal cytoplasm. The origin of the antigens and their release are discussed.     

Analysis of density and epitopes of D antigen on the surface of erythrocytes from DEL phenotypic individuals carrying the RHD1227A allele

Background

The characteristics of the D antigen are important as they influence the immunogenicity of D variant cells. Several studies on antigenic sites have been reported in normal D positive, weak D and partial D cases, including a comprehensive analysis of DEL types in Caucasians. The aim of this study was to assess D antigen density and epitopes on the erythrocyte surface of Asian type DEL phenotypic individuals carrying the RHD1227A allele in the Chinese population.

Materials and methods

A total of 154 DEL phenotypic individuals carrying the RHD1227A allele were identified through adsorption and elution tests and polymerase chain reaction analysis with sequence-specific primers in the Chinese population. D antigen density on the erythrocyte surface of these individuals was detected using a flow cytometric method. An erythrocyte sample with known D antigen density was used as a standard. Blood samples from D-negative and D-positive individuals were used as controls. In addition, D antigen epitopes on the erythrocyte surface of DEL individuals carrying the RHD1227A allele were investigated with 18 monoclonal anti-D antibodies specific for different D antigen epitopes.

Results

The means of the median fluorescence intensity of D antigen on the erythrocyte membrane surface of D-negative, D-positive and DEL individuals were 2.14±0.25, 193.61±11.43 and 2.45±0.82, respectively. The DEL samples were estimated to have approximately 22 D antigens per cell. The samples from all 154 DEL individuals reacted positively with 18 monoclonal anti-D antibodies specific for different D antigen epitopes.

Discussion

In this study, D antigen density on the erythrocyte surface of DEL individuals carrying the RHD1227A allele was extremely low, there being only very few antigenic molecules per cell, but the D antigen epitopes were grossly complete.     

旋毛虫成虫三种抗原SDS-PAGE及Western-blot比较研究

目的研究大理猪源旋毛虫(Trichinella spiralis)成虫虫体可溶性抗原、表面抗原和排泄分泌抗原3种抗原的蛋白组分及其之间的差异,比较分析其免疫反应性。方法以十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和蛋白印迹对成虫3种抗原进行蛋白组分及其免疫反应性分析。结果十二烷基硫酸钠-聚丙烯酰胺凝胶电泳结果:虫体可溶性抗原显示29条蛋白带,分子量范围在112kDa~10kDa之间,其中主带13条;表面抗原显示4条主要蛋白带,分子量分别为50、48、40、34kDa;排泄分泌抗原显示17条蛋白带,分子量范围在120~14kDa之间,其中主带6条,分子量分别为120、64、43、40、35、33kDa。蛋白印迹结果:虫体可溶性抗原出现13条反应条带,其中分子量为81、40、37、33、30kDa的条带着色明显;表面抗原出现4条反应条带,其分子量分别为50、48、40、34kDa;排泄分泌抗原显示7条反应带,其中43、40、27、18kDa着色明显。结论旋毛虫成虫虫体可溶性抗原与排泄分泌抗原较表面抗原蛋白组分复杂,3者主带部分属低分子量区;免疫反应性的强度表面抗原和排泄分泌抗原高于虫体可溶性抗原,说明前两种抗原是旋毛虫成虫刺激机体产生免疫应答的主要靶抗原。     

Carcinoembryonic antigen: its value in the follow-up of patients with colorectal cancer

We examined the value of carcinoembryonic antigen (CEA) monitoring for detecting treatable recurrence of colorectal carcinoma. CEA assays were undertaken in 193 patients over a 2-year period. The levels in 34 patients were raised in one or more assays above the laboratory-defined upper limit of normal; 31 cases were reviewed retrospectively. In 10% of patients there were Dukes' A lesions at the initial resection, in 39% Dukes' B, and in 52% Dukes' C1 or C2. Tumours were rectal in 61%. Median follow-up was 3 years (range, 16 years–2 months). In 23 of 31 (74%) there were symptoms or signs of recurrent disease prior to or simultaneously with an observed rise in CEA; in 8 the CEA rise preceded the onset of symptoms or the appearance of signs. Of the 31 cases 26 underwent investigation for recurrent disease, but in only 6 of these was the investigation driven by the observed rise in CEA rather than the onset of symptoms or presence of signs. Three of these six were false-positive results (50%), one has been lost to follow-up, and two had confirmed recurrence. Neither of the two with recurrence had operable disease. One of the two had no further treatment, and one underwent laparotomy at which multiple peritoneal seedlings were found. In both of the two cases going to laparotomy, one of which was prompted by a high CEA, widely disseminated disease was found. Over a 2-year period, serial CEA measurement thus yielded no patient benefit. Accepted: 13 October 1998     

日本血吸虫尾蚴成虫及虫卵的早期诊断组分抗原分析

目的寻找具有血吸虫病早期诊断价值的组分抗原.方法以感染后不同时间的兔血清,用SDS-聚丙烯酰胺凝胶电泳（SDS-PAGE）和免疫印迹试验（Western blotting）方法,对日本血吸虫尾蚴、成虫和虫卵中的可溶性抗原的成分进行免疫分析.结果可溶性尾蚴抗原（SCA）94、48、41、40 kDa和38 kDa组分抗原最早出现免疫印迹反应,能被感染后2周兔血清所识别,可被感染后3周兔血清识别的SCA 71、23 kDa组分抗原反应最强.可溶性成虫抗原（AWA）最早出现反应的组分抗原是71、58 kDa,能被感染后3周兔血清所识别.可溶性虫卵抗原（SEA）最早出现反应的组分抗原是270、151、73、69、50 kDa和24 kDa,能被感染后4周兔血清所识别.结论 SCA 94、71、48、41、40、38、23 kDa,AWA 71、58 kDa和SEA 270、151、73、69、50、24 kDa能被急性感染兔血清所识别,是具有潜在早期诊断价值的组分抗原.     

An antigenic peptide produced by reverse splicing and double asparagine deamidation

A variety of unconventional translational and posttranslational mechanisms contribute to the production of antigenic peptides, thereby increasing the diversity of the peptide repertoire presented by MHC class I molecules. Here, we describe a class I-restricted peptide that combines several posttranslational modifications. It is derived from tyrosinase and recognized by tumor-infiltrating lymphocytes isolated from a melanoma patient. This unusual antigenic peptide is made of two noncontiguous tyrosinase fragments that are spliced together in the reverse order. In addition, it contains two aspartate residues that replace the asparagines encoded in the tyrosinase sequence. We confirmed that this peptide is naturally presented at the surface of melanoma cells, and we showed that its processing sequentially requires translation of tyrosinase into the endoplasmic reticulum and its retrotranslocation into the cytosol, where deglycosylation of the two asparagines by peptide-N-glycanase turns them into aspartates by deamidation. This process is followed by cleavage and splicing of the appropriate fragments by the standard proteasome and additional transport of the resulting peptide into the endoplasmic reticulum through the transporter associated with antigen processing (TAP).     

血清CA19—9、CEA、CA125联合检测诊断食管癌的价值

目的探讨多抗原联合检测诊断食管癌的价值。方法应用全自动化学免疫分析检测254例食管癌患者、40例食管炎患者和100例健康体检者血清CA19-9、CEA、CA125的表达。结果三项指标联合检测诊断食管癌的灵敏度和特异度均明显高于单独检测及任两项联合检测（P均〈0．01）。结论三项指标联合检测可提高诊断食管癌的灵敏度和特异度,有利于早期诊断食管癌。