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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

基本信息

批准号：
7627967
负责人：
HENRY A ERLICH
金额：
$ 53.53万
依托单位：
CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-20 至 2010-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7627967
关键词：
Accounting Affect Alleles Amino Acids Antibodies Antigens Autoantigens Autoimmune Diseases Autoimmunity Binding Biological Assay Candidate Disease Gene Caucasians Caucasoid Race Cell surface Cells Chronic Communicable Diseases Complementarity Determining Regions Complex Crohn&apos s disease Cytotoxic T-Lymphocytes DEK gene Data Disease Disease Association Disease susceptibility Doctor of Philosophy Epitopes Equilibrium Etiology Exons Functional disorder Genes Genetic Genetic Determinism Genetic Polymorphism Genetic Predisposition to Disease Genetic Risk Genotype Goals HIV HLA Antigens Haplotypes Hematopoietic Hepatitis Human Genome Immune Immune response Immune system Immunogenetics Immunoglobulins Immunologics Individual Inflammatory Insulin-Dependent Diabetes Mellitus Intestines Laboratories Ligands Linkage Disequilibrium Methods Microbe Molecular Mutation Natural Killer Cells Nature Oligonucleotides PTPN22 gene Patients Peptides Phenotype Play Population Predisposition Prevalence Principal Investigator Protein Tyrosine Phosphatase Proteins Pseudogenes Psoriasis Psoriatic Arthritis Receptor Gene Recording of previous events Reporting Research Personnel Resolution Rheumatoid Arthritis Risk Risk Factors Role Sampling Scleroderma Stratification T-Cell Receptor T-Lymphocyte Testing Time Variant Work base case control cohort cytokine design disorder control immune function killer immunoglobulin-like receptor microbial microorganism antigen pathogen population based receptor response trait

项目摘要

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类基因座的特定等位基因和单倍型与多种自身免疫性疾病的相关性已得到充分证实。最近，已报道编码NK细胞上的刺激性和抑制性受体的杀伤免疫球蛋白样受体（KIR）基因的多态性与一些相同的HLA相关疾病（例如银屑病关节炎、硬皮病和T1 D）相关。这些受体中的许多所识别的配体是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的HLA I类和II类基因座的基因分型和高通量MALDI-TOF方法的KIR基因座的基因分型。特定的DRB 1等位基因已经与这些疾病中的每一种相关（CD的DRB 1 *0103和RA的DRB 1 *0401和 *0404），但我们将评估其他HLA基因座在这些疾病中的作用。HLA I类分型在评估KIR基因的作用中也是至关重要的，因为相关数据必须根据HLA表位配体的存在或不存在来分层，以检查KIR-HLA组合的作用。此外，我们还将对另一种已确立的疾病基因多态性PTNP 22位点进行基因分型，从而对HLA和KIR相关数据进行分层。基于人群的研究中的HLA-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。