HLA GENES & HYBRID MOLECULES IN PARTICULAR JRA

HLA基因

• 批准号: 3456878
• 负责人: BARBARA S NEPOM
• 金额: $ 11.58万
• 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/3456878
• 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 sequence; population genetics; 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性关节炎（Pauci I JRA）