HLA AS A PREDICTOR FOR STROKE IN SICKLE CELL ANEMIA

描述（来自申请人摘要的逐字）：中风是最常见的中风之一。 镰状细胞性贫血（SCA）儿童的毁灭性并发症。镰状 细胞性贫血是儿童中风的最常见原因， SCA患者在MRI扫描上有脑梗死的证据。大多数 SCA儿童的中风是进行性脑梗死的结果， 颅内大血管狭窄，但其病理生理学基础 这些病变是未知的。在一项初步研究中，我们记录了 特定的人类白细胞抗原（HLA）表型与 SCA患儿脑梗死风险增加。的目标 本研究的目的是通过确定 特定的HLA等位基因或HLA单倍型是否会增加 SCA儿童脑梗死。此外，HLA之间的关联 等位基因和梗死类型（大血管vs.小血管，无症状vs.症状） 将被探索。将对储存的DNA样本进行分子HLA分型 来自之前入组两个大型研究的SCA患者， 多机构试验，镰状细胞性贫血中风预防试验 （STOP）和镰状细胞病合作研究（CSSCD）。所有这些 患者接受盲法MRI扫描作为这些试验中招募的一部分。 脑梗死患者的HLA表型频率 梗死将与MRI阴性的SCA患者进行比较 治疗梗塞这些发现可能会对儿童产生深远的影响， SCA，因为HLA分型可以用作识别这些患者的标志物， 中风的风险更高。早期识别这些患者将有助于 预防性干预措施在那些有中风风险和避免 在那些风险降低的患者中使用潜在毒性治疗。

DESCRIPTION (Verbatim from the Applicant's Abstract): Stroke is one of the most devastating complications in children with sickle cell anemia (SCA). Sickle cell anemia is the most common cause of stroke in childhood and 25% of children with SCA have evidence of cerebral infarction on MRI scanning. The majority of strokes in children with SCA are the result of infarction from progressive narrowing of the large intracranial vessels, but the pathophysiology underlying these lesions is unknown. In a preliminary study, we have documented that particular Human Leukocyte Antigen (HLA) phenotypes are associated with an increased risk of cerebral infarction in children with SCA. The objective of this research is to confirm and expand this preliminary study by ascertaining whether particular HLA alleles or HLA haplotypes confer an increased risk of cerebral infarction in children with SCA. In addition, associations between HLA alleles and type of infarction (large vs. small vessel, silent vs. symptomatic) will be explored. Molecular HLA typing will be performed on stored DNA samples from patients with SCA who were previously enrolled in two large multi-institution trials, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and the Cooperative Study of Sickle Cell Disease (CSSCD). All of these patients underwent blinded MRI scanning as part of enrollment in these trials. The HLA phenotypic frequencies of SCA patients with MRI-documented cerebral infarction will be compared with those of SCA patients whose MRI is negative for infarction. These findings could have a profound impact on children with SCA, as HLA typing could be used as a marker in identifying those patients at higher risk for stroke. Early identification of these patients would allow for preventive interventions in those at risk for stroke and avoidance of potentially toxic therapies in those at reduced risk.