HLA GENES & HYBRID MOLECULES IN PAUCIARTICULAR JRA

HLA基因

• 批准号: 3456879
• 负责人: BARBARA S NEPOM
• 金额: $ 10.93万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3456879
• 关键词: alleles; antinuclear autoantibody; autoimmune disorder; autoradiography; biological polymorphism; complementary DNA; disease /disorder proneness /risk; flow cytometry; gel electrophoresis; gene complementation; heterozygote; high performance liquid chromatography; histocompatibility antigens; human population genetics; human tissue; juvenile rheumatoid arthritis; major histocompatibility complex; molecular pathology; monoclonal antibody; neoplastic transformation; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; population genetics; protein structure; radiation genetics; structural genes; surface antigens; uveitis

Pauciarticular juvenile rheumatoid arthritis Type I (Pauci I JRA) is a relatively common inflammatory disease of childhood which, like a large number of "autoimmune" diseases, is associated with certain HLA Class II specificities. A number of investigators has demonstrated the association of this form of JRA with the HLA determinants DR5, 6, and/or 8, although the basis of this association is not understood. A growing body of information has advanced our understanding of the complexity of genetic haplotypes represented by each serologically-defined HLA determinant. For example, we have previously shown that the specificity HLA-DR4 actually encompasses at least 5 different expressed polypeptides encoded by the DR locus genes; the closely-linked specificity HLA-DQw3 likewise contains at least 3 electrophoretically distinct proteins and a larger number of restriction fragment length polymorphisms (RFLP), indicating broad nucleotide variation. Similar complexity of the Pauci I JRA-associated specifications HLA-DR5, 6, and 8 is emerging. We hypothesize that a common structural basis exists among the HLA Class II specificities associated with Pauci I JRA. The objectives of this study are to identify certain serologic and structural polymorphisms within these disease-associated haplotypes which may account for their correlation with disease; to determine whether the presence of more than one HLA- encoded element increases disease risk, and, if so, whether this represents gene complementation; and to investigate the possible predictive value of certain structural polymorphisms to particular clinical manifestations, such as the presence of uveitis.

少关节幼年型类风湿关节炎I型（Pauci I JRA） 是一种相对常见的儿童炎症性疾病， 就像大量的“自身免疫”疾病一样， 某些HLA II类特异性 一些调查人员已经 证明了这种形式的JRA与HLA 决定因素DR 5，6和/或8，虽然这个基础 关联不被理解。 越来越多的信息促进了我们对 每种单倍型所代表的遗传单倍型的复杂性 血清学定义的HLA决定簇。 比如我们有 以前的研究表明，HLA-DR 4的特异性实际上 包括至少5种不同的表达多肽， DR位点基因;紧密连锁特异性HLA-DQw 3 同样含有至少3种不同的蛋白质 和大量的限制性片段长度多态性 （RFLP），表明广泛的核苷酸变异。 相似的复杂性 在Pauci I JRA相关规范HLA-DR 5、6和8中， 正在浮现 我们假设，一个共同的结构基础之间存在的 与Pauci I型JRA相关的HLA II类特异性 的 本研究的目的是确定某些血清学和 这些疾病相关的结构多态性 可能解释其与疾病相关性的单倍型; 以确定是否存在多于一个的HLA- 编码的元素会增加疾病风险，如果是这样， 代表基因互补;并研究可能的 某些结构多态性对特定 临床表现，如葡萄膜炎的存在。