Mutations in the SIAE Gene and Susceptibility to Autoimmune Diseases

项目负责人/主要研究者（最后一名、第一名、中间名）：1 R 01 AI 076505 - 01 A2 PI姓名：PILLAI，SHIV S 摘要 修饰唾液酸部分的酶称为唾液酸乙酰酯酶，调节来自B淋巴细胞上抗原受体的信号强度。这种基因在小鼠中的突变导致增强的B细胞受体信号传导和自身免疫-小鼠发展成狼疮样综合征。 这种酯酶的突变在自身免疫性患者中发现频率很高。这些功能丧失变异在系统性红斑狼疮和类风湿性关节炎等疾病患者中相对常见，但在对照组中不常见。我们试图评估大量患者和对照中这些突变的频率，检查家族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体结构，并在基于细胞系的研究中检查突变以显性阴性方式发挥作用的可能性。

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.