The Role of HLA and KIR in Rheumatoid Arthritis and Crohn's Disease

HLA 和 KIR 在类风湿关节炎和克罗恩病中的作用

• 批准号: 7123905
• 负责人: HENRY A ERLICH
• 金额: $ 44.52万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123905
• 关键词: Crohn' s disease; clinical research; genetic polymorphism; genetic screening; genetic susceptibility; genotype; high throughput technology; human tissue; immunologic receptors; major histocompatibility complex; matrix assisted laser desorption ionization; natural killer cells; rheumatoid arthritis

DESCRIPTION (provided by applicant): The association of specific alleles and haplotypes at the HLA class I and class II loci with a variety of autoimmune diseases is well established. Recently, polymorphisms in the Killer Immunoglobulin-like Receptors (KIR) genes that encode the stimulatory and inhibitory receptors on NK cells have been reported to be associated with a few of the same HLA-associated diseases, (e.g. psoriatic arthritis, scleroderma, and T1D). The ligands recognized by many of these receptors are epitopes on HLA class I molecules. Our goal is to carry out case/control association analyses for Crohn's Disease and Rheumatoid Arthritis using our high resolution HLA and KIR genotyping methods. We have developed high throughput, robust, and high resolution immobilized probe methods for genotyping the HLA class I and class II loci and a high throughput MALDI-TOF method for genotyping the KIR loci. Specific DRB1 alleles have already been associated with each of these diseases (DRB1*0103 for CD and DRB1*0401 and *0404 for RA) but we will evaluate the role of other HLA loci in these diseases. HLA class I typing is also critical in evaluating the role of the KIR genes since the association data must be stratified on the presence or absence of the HLA epitope ligand to examine the effects of KIR-HLA combinations. In addition, we will genotype another well-established disease gene polymorphism, the PTNP22 locus, allowing stratification of the HLA and KIR association data. The analyses of HLA-KIR in population-based studies will add significantly to our understanding of the role of the innate immune system in these complex autoimmune disorders.

描述(由申请人提供)：人类白细胞抗原I类和II类基因座上的特定等位基因和单倍型与各种自身免疫性疾病之间的关联已得到很好的证实。最近，编码NK细胞上刺激受体和抑制受体的KIR基因的多态性被报道与一些相同的人类白细胞抗原相关疾病(如银屑病关节炎、硬皮病和T1D)有关。其中许多受体识别的配体是人类白细胞抗原I类分子上的表位。我们的目标是使用我们的高分辨率HLA和KIR基因分型方法进行克罗恩病和类风湿性关节炎的病例/对照关联分析。我们已经开发出高通量、可靠和高分辨率的固定化探针方法，用于人类白细胞抗原I类和II类基因座的基因分型，以及高通量的MALDI-TOF方法，用于KIR基因座的基因分型。已经发现DRB1等位基因与这些疾病相关(CD的DRB1*0103和RA的DRB1*0401和*0404)，但我们将评估其他HLA基因座在这些疾病中的作用。在评估KIR基因的作用时，人类白细胞抗原I类分型也是至关重要的，因为关联数据必须根据是否存在人类白细胞抗原表位配体来分层，以检查KIR-人类白细胞抗原组合的影响。此外，我们还将对另一个公认的疾病基因多态--PTNP22基因座进行基因分型，从而对人类白细胞抗原和KIR的关联数据进行分层。在基于人群的研究中对人类白细胞抗原-KIR的分析将大大增加我们对先天免疫系统在这些复杂的自身免疫性疾病中的作用的理解。