DISEASE SUSCEPTIBILITY GENES IN PEDIATRIC ANTIPHOSPHOLIPID ANTIBODY SYNDROME

抗磷脂抗体综合征是一种血栓性疾病 其特征在于血栓形成与针对 对抗磷脂 除了蛋白C蛋白S抗凝血酶 III缺乏和因子V Leiden突变，APS构成了一个 儿童血栓形成的重要原因，往往是没有认识到的 被儿科医生。 APS作为继发性疾病存在于 与系统性红斑狼疮（SLE）相关，并作为原发性 在没有潜在风湿性疾病的情况下的综合征。 抗磷脂抗体（aPL）是异质性的，可以是 通过几种不同的检测方法检测。 虽然这种综合症 近年来在文献中受到越来越多的关注， 关于抗体检测、抗原性 靶向、诊断、发病机制和适当临床管理。 此外，在诊断、预后、 和儿科人群的管理。 II类主要 组织相容性复合体（MHC）基因编码的分子涉及 具有自我和非自我的区分， 免疫活化和调节T细胞识别。 II类 MHC基因以前与疾病易感性相关 对于其他几种风湿性和非风湿性疾病， investigators. 有证据表明，II类MHC相关性可能 存在的aPL的表达和APS的后续发展， 成人，并没有在儿童中广泛研究。 不是所有 患有循环性aPL的个体随后发展为APS。 和 最近，β 2-糖蛋白I已被证明是重要的 在检测血栓形成个体的aPL方面。 证据支持第五结构域的磷脂结合作用， 因此该区域的多态性可能与APS有关。 的 该项目的目的是确定疾病易感基因， 可能表征一个亚组的儿童在增加的风险， 血栓形成的发展，并可能有助于增加 了解这种疾病的发病机制。

Antiphospholipid antibody syndrome (APS) is a thrombotic disorder characterized by the association of thrombosis with antibodies directed against phospholipids. In addition to protein C, protein S, antithrombin III deficiency, and Factor V Leiden mutation, APS constitutes a significant cause of thrombosis in children that is often no recognized by pediatricians. APS exists both as a secondary disorder in association with systemic lupus erythematosus (SLE), and as a primary syndrome in the absence of underlying rheumatic disorders. Antiphospholipid antibodies (aPL) are heterogeneous and can be detected by several different assays. Although the syndrome has received increased attention in the literature in recent years, there are still many unanswered questions regarding antibody detection, antigenic target, diagnosis, pathogenesis, and appropriate clinical management. Furthermore, there are unique issues regarding diagnosis, prognosis, and management in the pediatric population. Class II Major Histocopatibility Complex (MHC) genes encode molecules involved with the discrimination of self and non-self, presentation of antigen for immuneactivation, and modulation of T cell recognition. Class II MHC genes have previously been correlated with disease susceptibility for several rheumatic and non-rheumatic disorders by other investigators. Evidence suggests that Class II MHC associations may exist for the expression of aPL and subsequent development of APS in adults, and has not been studied extensively in children. Not all individuals with circulating aPL subsequently develop APS. And recently, Beta 2-Glycoprotein I has been demonstrated to be important in the detection of aPL from individuals who do develop thromboses. Evidence supports a phospholipid binding role for the fifth domain, and thus polymorphism of this region may be associated with APS. The purpose of this project is to identify disease susceptibility genes which may characterize a subgroup of children at increased risk for the development of thrombosis, and potentially contribute to an increased understanding of the pathogenesis of this disorder.