中国正常人及类风湿关节炎病人MHC－Ⅱ类DR＿4亚型基因核苷酸序列初步分析

对中国人群正常人及类风湿关节炎病人ＤＲ＿４亚型基因决定型别特异性的第二个外显子进行体外扩增、克隆及序列分析显示，６例正常人及３例类风湿关节炎病人存在三种ＤＲ＿４亚型（ＤＲＢｌ０４０２，ＤＲＢｌ０４０５，ＤＲＢｌ．０４０６），中国人这三种亚型第二个外显子核苷酸序列与白种人一致。序列分析结果为进一步应用常规ＰＣＲ－ＳＳＯ法及ＰＣＲ－ＲＦＬＰ法进行中国人ＤＲ＿４基因定型提供了依据。此外，还将序列分析结果与ＰＣＲ－ＳＳＯ杂交分析结果进行了比较，具备较全面的覆盖各亚型多态性区域的探针可以减少等位基因同源性干扰，减少分型误差     

MHC—Ⅱ类基因启动子及其多态性Ⅰ——顺式作用DNA元件研究进展

ＭＨＣ－Ⅱ类基因在免疫应答的调控中起着关键的作用，人类ＨＬＡ－Ⅱ类基因位于第６号染色体上ＭＨＣ复合体的Ｄ区，近年来国外已在一些Ⅱ类基因启动子区发现有多态性，且这种多态性在Ⅱ类基因中普遍存在，这不仅说明Ⅱ类基因启动子本身的调节活性十分复杂，也深化了对Ⅱ类分子表达调控的认识。本文以Ⅱ类基因启动子的结构为基础对启动子顺式作用元件的多态性作一综述。     

HLA-DR4与类风湿关节炎的相关性探讨

目的探讨HLA-DR4与类风湿关节炎(RA)的相关性.方法采用特异性引物聚合酶链反应方法对广东地区汉族人群52例类风湿关节炎患者及100例正常健康者的HLA-DR4基因进行分析,并测定其基因频率.结果 HLA-DR4基因在52例类风湿关节炎患者中的基因频率(48.1%)显著高于其在100例正常对照组中的基因频率(19.6%,p<0.01).结论 HLA-DR4基因与广东地区人群的类风湿关节炎易感性有关联.     

HLA-DR4与类风湿关节炎的相关性探讨

目的　探讨HLA -DR4与类风湿关节炎 (RA)的相关性 .方法　采用特异性引物聚合酶链反应方法对广东地区汉族人群 5 2例类风湿关节炎患者及 10 0例正常健康者的HLA -DR4基因进行分析 ,并测定其基因频率 .结果HLA -DR4基因在 5 2例类风湿关节炎患者中的基因频率 (4 8.1% )显著高于其在 10 0例正常对照组中的基因频率(19.6 % ,p<0 .0 1) .结论　HLA -DR4基因与广东地区人群的类风湿关节炎易感性有关联     

中国南京地区汉族人HLA－DR4DNA的快速分型

应用ＡＲＭＳ（ａｍｐｌｉｆｉｃａｔｉｏｎｒｅｆｒａｃｔｏｒｙｒｎｕｔａｔｉｏｎｓｙｓｔｅｍ）方法对南京地区１００例汉族健康人ＨＬＡ－ＤＲ４进行基因分型，结果表明，本地区汉族人ＨＬＡ－ＤＲ４基因纯合子占６％，杂合子占１５％，非ＤＲ４占７９％。本法较ＰＣＲ／ＳＳＯ法简单、快速，结果可靠，可用于ＨＬＡ配型。检测结果为ＨＬＡ相关联疾病及人类学的研究提供了参考依据。     

MHC－Ⅱ类基因启动子及其多态性Ⅰ──顺式作用DNA元件研究进展

ＭＨＣ－Ⅱ类基因在免疫应答的调控中起着关键的作用。人类ＨＬＡ－Ⅱ类基因位于第６号染色体上ＭＨＣ复合体的Ｄ区，近年来国外已在一些Ⅱ类基因启动子区发现有多态性，且这种多态性在Ⅱ类基因中普遍存在，这不仅说明Ⅱ类基因启动子本身的调节活性十分复杂，也深化了对Ⅱ类分子表达调控的认识。本文以Ⅱ类基因启动子的结构为基础对启动子顺式作用元件的多态性作一综述。     

HLA—DR基因多态性与广东汉族泛发型白癜风患者的相关性研究

目的研究广东籍汉族泛发型白癜风患者与HIA—DR的相关性。方法采用聚合酶链反应一序列特异性引物（PCR．SSP）技术，对30例广东籍汉族泛发型白癜风患者和30例健康对照者静脉血样本HLA-DR等位基因多态性进行研究。结果泛发型白癜风患者DRB1^＊0701等位基因频率显著升高（RR=5．216，PC〈0．05），DRw52（DRB3^＊0101／02DRB3^＊0201DRB3^＊0301）、DRw53（DRB4^＊0101／03／05）和DRw51（DRB5^＊0101／02DRB5^＊0202）基因频率明显低于正常组，以上三者两组间比较均有显著性差异（PC〈0．05）。结论HIJA—DRB1^＊0701等位基因可能与广东籍汉族泛发型白癜风的发病有关，而DRw52（DRB3^＊0101／02DRB3^＊0201DRB3^＊0301）、DRw53（DRB4^＊0101／03／05）和DRw51（DRB5^＊0101／02DRB5^＊0202）对泛发型白癜风发病可能有一定保护作用。     

Dw subtypes of DR4 in rheumatoid arthritis: evidence for a preferential association with Dw4

We have determined the frequency of the DR4-associated Dw subtypes, defined by homozygous typing cells, in a group of rheumatoid arthritis (RA) patients on second-line drug therapy. The frequency of DR4 in these patients was 86%. Among Caucasians, the frequency of Dw4 in the DR4-positive patients was significantly increased (68%) as compared to DR4-positive normal individuals (46%; p less than 0.025). Dw4, as compared to the other DR4 subtypes tested, may also be associated with more severe disease as judged by indices of functional impairment and joint damage. In a small subgroup of non-Caucasian (black and Native American) patients, the Dw13 (DB3) subtype of DR4 was often seen, suggesting that RA may have different Dw associations in different ethnic groups.     

DR4 related antisera pattern differences in insulin dependent diabetes mellitus and rheumatoid arthritis

Three allosera patterns of reactivity are described which appear to define subtypes of DR4 and segregate in families with different DR4 bearing haplotypes. There appears to be a preponderance of one particular subtype (termed DR4.3) occurring in type 1 insulin dependent diabetes mellitus, while in rheumatoid arthritis the distribution of subtypes within DR4 individuals is similar to that seen in controls. Although we refer to DR4 subtypes the proof that these sera are detecting a determinant on the DR molecule and not a product of another locus, an allele of which is linkage disequilibrium with DR4, awaits immunochemical confirmation.     

Molecular mechanisms involved in the association of HLA-DR4 and rheumatoid arthritis

Susceptibility to developing rheumatoid arthritis (RA) maps to a highly conserved amino acid motif located in the third hypervariable region of different HLA-DRB1 chains. This motif, namely QKRAA, QRRAA, or RRRAA, helps the development of RA by an unknown mechanism. The QKRAA motif predisposes to more severe disease than the QRRAA or RRRAA motifs. The QKRAA motif carries particular properties: it is a strong B- and T-cell epitope, it shapes the T cell repertoire, it is overrepresented in protein databases, and it is a binding motif for bacterial and human 70-kDa heat-shock proteins. In this article, we propose different models to explain how the QKRAA motif might contribute to RA.     

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

Studies on the relationship between HLA DR4 and in vitro IgM rheumatoid factor production

The relationship between the presence of the DR4 antigen and other HLA antigens and in vitro production of IgM-rheumatoid factor by lymphocytes from a group of healthy young subjects was examined. Pokeweed and Epstein--Barr virus-stimulated lymphocyte cultures were examined for the production of rheumatoid factor and immunoglobulins. No significant correlation was found between the presence of the DR4 antigen and in vitro production of IgM rheumatoid factor. The presence of the B18 antigen seemed to identify a population of nonresponders when stimulated with PWM.     

HLA-DQ beta 3.1 allele is a determinant of susceptibility to DR4-associated rheumatoid arthritis

Rheumatoid arthritis is associated with HLA-DR4 in several ethnic groups. Since DR4 haplotypes encode a diverse array of class II molecules, it is of interest to characterize the nature of the primary association. We have examined molecular polymorphisms of HLA class II gene products expressed by normals and rheumatoid arthritis patients using monoclonal antibodies and two-dimensional electrophoresis. Most homozygous DR4 rheumatoid arthritis patients express DR beta 1 molecules associated with Dw4 or Dw14 mixed lymphocyte culture determinants. In Caucasoids, two DR4-linked DQw3-associated beta-chain alleles are defined by two-dimensional electrophoresis. These variants, designated DQ beta 3.1 and 3.2, are associated with the serologic determinants DQw7 and DQw8, respectively. A panel of 40 DR4-positive normals was also examined for nucleotide sequence polymorphisms associated with DQB3.1 and 3.2 genes using the polymerase chain reaction and specific oligonucleotide probes. At the DQ beta level the rheumatoid arthritis panel was distinguished by enrichment for the DQ beta 3.1 allele with 100% of patients positive for DQw7. Results presented here suggest that specific DQ beta alleles may modify the effect of HLA-DR4 beta 1 alleles in conferring susceptibility to rheumatoid arthritis in a phenotype-specific fashion.