Mutations in the SIAE Gene and Susceptibility to Autoimmune Diseases

SIAE 基因突变与自身免疫性疾病的易感性

基本信息

批准号：
7847524
负责人：
SHIV Subramaniam PILLAI
金额：
$ 44.25万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-22 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7847524
关键词：
Acetylation Antibodies Antibody Formation Antigen Receptors Autoimmune Diseases Autoimmune Process Autoimmunity B-Lymphocytes CD22 gene Carbohydrates Cell Line Clinical Distribution Code Development Disease Dominant-Negative Mutation Employee Strikes Enzymes Esterase Gene Etiology Exhibits Family Family Study Frequencies Gene Mutation Genes Human Immune Complex Glomerulonephritis Immune system Knowledge Link Molecular Mus Mutation Names Nuclear PTPN6 gene Patients Positioning Attribute Predisposition Principal Investigator Proteins Receptor Signaling Receptors, Antigen, B-Cell Rheumatoid Arthritis Sialic Acids Signal Transduction Structure Susceptibility Gene Syndrome Systemic Lupus Erythematosus Testing Therapeutic Variant abstracting base cohort disease-causing mutation disorder control enzyme structure esterase human disease loss of function lupus-like mutant novel peripheral tolerance programs protein misfolding public health relevance receptor function sialic acid binding Ig-like lectin simian human immunodeficiency virus stoichiometry

项目摘要

Program Director/Principal Investigator (Last, First, Middle): 1R01AI076505 - 01A2 PI Name: PILLAI, SHIV S ABSTRACT An enzyme that modifies sialic acid moieties known as Sialic acid acetyl esterase regulates the strength of signaling from the antigen receptor on B lymphocytes. Mutation of this gene in mice leads to enhanced B cell receptor signaling and autoimmunity - the mice develop a lupus like syndrome. Mutations in this esterase have been found at a high frequency in patients with autoimmunity. These loss of function variants are relatively common in patients with systemic lupus erythematosus and rheumatoid arthritis among other conditions, but are infrequent in controls. We seek to assess the frequency of these mutations in large numbers of patients and controls, examine families to determine how penetrant these mutations are and examine the mechanisms by which these mutations cause disease. The actual oligomeric structure of the enzyme will be determined and the possibility that mutations function in a dominant negative manner will be examined in cell line based studies.

项目总监/首席调查员（最后一个，中间，中间）：1R01AI076505-01A2 PI名称：Pillai，Shiv S 抽象的一种修饰称为唾液酸乙酰酯酯酶的唾液酸部分的酶调节B淋巴细胞上抗原受体的信号强度。该基因在小鼠中的突变导致B细胞受体信号传导和自身免疫性增强 - 小鼠形成狼疮综合征。在自身免疫性患者中，该酯酶中的突变在高频中发现。这些功能变异的丧失在全身性红斑狼疮和类风湿关节炎的患者中相对常见，但在对照中很少见。我们试图评估大量患者和对照组中这些突变的频率，检查家庭以确定这些突变的渗透性，并检查这些突变引起疾病的机制。将确定酶的实际寡聚结构，并在基于细胞系的研究中检查突变以显性阴性方式起作用的可能性。