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: 7007787
• 负责人: HENRY A ERLICH
• 金额: $ 24.01万
• 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/7007787
• 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）：HLA I类和II类位点的特定等位基因和单倍型与多种自身免疫性疾病的关联已经得到证实。最近，在NK细胞上编码刺激和抑制受体的杀伤免疫球蛋白样受体（KIR）基因的多态性已被报道与一些相同的hla相关疾病（如银屑病关节炎、硬皮病和T1D）相关。许多这些受体识别的配体是HLA 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基因分型方法对克罗恩病和类风湿性关节炎进行病例/对照关联分析。我们已经开发了高通量，稳健，高分辨率的固定化探针方法用于HLA I类和II类位点的基因分型，以及高通量MALDI-TOF方法用于KIR位点的基因分型。特定的DRB1等位基因已经与这些疾病相关（CD的DRB1*0103和RA的DRB1*0401和*0404），但我们将评估其他HLA位点在这些疾病中的作用。HLA I类分型对于评估KIR基因的作用也至关重要，因为相关数据必须根据HLA表位配体的存在或缺失进行分层，以检查KIR-HLA组合的影响。此外，我们将对另一种已建立的疾病基因多态性PTNP22位点进行基因分型，从而对HLA和KIR相关数据进行分层。在基于人群的研究中对HLA-KIR的分析将大大增加我们对先天免疫系统在这些复杂自身免疫性疾病中的作用的理解。