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

人类白细胞抗原I、II类基因座特定等位基因和单倍型与多种疾病的关联 自身免疫性疾病由来已久。近年来，杀伤细胞免疫球蛋白样多态的研究进展 已有报道编码NK细胞上的刺激受体和抑制受体的受体(KIR)基因 与几种与人类白细胞抗原相关的疾病有关(如银屑病关节炎、硬皮病和 T1D)。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 是利用我们的HIGH进行克罗恩病和类风湿性关节炎的病例/对照关联分析 解决人类白细胞抗原和KIR基因分型方法。我们开发了高吞吐量、健壮和高性能 HLAI、II类基因座基因分型的分辨率固定探针方法及高通量 MALDI-TOF法用于KIR基因座的基因分型特定的DRB1等位基因已经被认为与 这些疾病中的每一种(CD的DRB1*0103和RA的DRB1*0401和*0404)，但我们将评估其作用 这些疾病中的其他人类白细胞抗原基因座。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 由于关联数据必须根据存在或不存在HLA表位配体来分层 检查KIR-人类白细胞抗原组合的效果。此外，我们还将对另一种公认的疾病进行基因分型。 基因多态，PTNP22基因座，允许对人类白细胞抗原和KIR关联数据进行分层。这个 在以人群为基础的研究中对人类白细胞抗原KIR的分析将极大地增加我们对人类免疫缺陷病毒 先天免疫系统在这些复杂的自身免疫性疾病中。

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, (eg 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 *0404for 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.