HLA GENES & HYBRID MOLECULES IN PAUCIARTICULAR JRA

HLA基因

• 批准号: 3456881
• 负责人: BARBARA S NEPOM
• 金额: $ 11.26万
• 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/3456881
• 关键词: alleles; antinuclear autoantibody; autoimmune disorder; autoradiography; complementary DNA; disease /disorder proneness /risk; flow cytometry; gel electrophoresis; gene complementation; genetic polymorphism; 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; transcription factor; 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.

少关节幼年类风湿性关节炎I型(少关节I JRA) 是一种比较常见的儿童期炎症性疾病， 就像大量的“自身免疫性”疾病一样， 某些人类白细胞抗原II类的特异性。一些调查人员已经 证明了这种形式的JRA与人类白细胞抗原的关联 行列式DR5、6和/或8，尽管它的基础 协会是不被理解的。 越来越多的信息促进了我们对 各自所代表的遗传单倍型的复杂性 血清学定义的人类白细胞抗原决定簇。例如，我们有 以前的研究表明，人类白细胞抗原-DR4的特异性实际上 包含至少5个编码的不同表达多肽 由DR基因座基因决定的；紧密连锁的特异性HLA-DQw3 同样含有至少3种电泳性不同的蛋白质 以及大量的限制性片段长度多态 (RFLP)，表明广泛的核苷酸变异。相似的复杂性 在PAUCI I JRA相关规范中，HLA-DR5、6和8是 正在浮现。 我们假设，在 与Pauci I JRA相关的人类白细胞抗原II类特异性。这个 这项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 可能与疾病相关的单倍型； 以确定是否存在一个以上的人类白细胞抗原- 编码元素会增加疾病风险，如果是这样，这是否会 代表基因互补；并调查可能的 某些结构多态对特定基因的预测价值 临床表现，如葡萄膜炎的存在。