HLA/KIR Region Genetics in Pediatric Arthritis

小儿关节炎中的 HLA/KIR 区域遗传学

• 批准号: 7125044
• 负责人: DAVID N. GLASS
• 金额: $ 43.91万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125044
• 关键词: adolescence (12-20); cell surface receptors; child (0-11); clinical research; cooperative study; family genetics; gene expression; genetic mapping; genetic susceptibility; high throughput technology; human genetic material tag; human subject; juvenile rheumatoid arthritis; major histocompatibility complex; natural killer cells; single nucleotide polymorphism

JRA (also known as JIA) includes the commonest chronic autoimmune arthropathies of childhood. The MHC is involved with respect to risk, either susceptibility or protection in a subtype specific manner with strong gender bias' and differences between ethnicities. Multiple MHC effects have been shown, especially in the commonest subtype, so called early onset pauciarticular JRA (Persistent Oligo in the JIA terminology) with three or more MHC regions believed to interact in generating susceptibility. An additional feature of the disease, unlike some other forms of autoimmunity, is the relative absence of common extended or ancestral haplotypes, especially those carrying HLA-DR4 and HLA-DR7 both of which are protective. The three regions include a class I region, or an area telomeric to it, and two class II regions those around HLA DR/DQ and HLA-DP. None of the regions involved are well defined nor were the specific genes involved identified. The alleles marking these regions (HLA-DR8, 11 and HLA-DPB1*0201) are atypical for autoimmunity. This is therefore an unusual MHC contribution to autoimmunity, the elucidation of which lends itself to high throughput technologies. The genetic features, although involving arthritis, are quite distinct from adult rheumatoid arthritis except for about 5% of older children. It is proposed to construct high throughput SNP maps in a family based study. Subtypes have different MHC profiles and in the rarest and most severe form of disease, systemic onset JRA, the MHC effect is rather minimal. In this form, preliminary data involving KIR gene haplotypes is available. Pursuing these KIR gene observations is proposed. The ability to leverage ongoing pheontyping and family based sample collection ensures a large and continuously growing pool of available DMAs for this project. Some of the patients will also have extensive gene expression studies allowing a comprehensive approach to the MHC and KIR genes in JRA and its subtypes.

JRA（也称为JIA）包括儿童期最常见的慢性自身免疫性关节病。MHC与风险、易感性或保护有关，以一种特定亚型的方式存在强烈的性别偏见和种族差异。已经显示出多种MHC效应，特别是在最常见的亚型中，即所谓的早发性少关节性JRA (JIA术语中的持续性Oligo)，其中三个或更多MHC区域被认为在产生易感性方面相互作用。与其他形式的自身免疫性疾病不同，该病的另一个特征是相对缺乏共同延伸或祖先