HLA AS A PREDICTOR FOR STROKE IN SICKLE CELL ANEMIA

描述(逐字摘自申请者的摘要)：中风是最常见的 镰状细胞性贫血(SCA)儿童的破坏性并发症。镰刀 细胞性贫血是儿童中风最常见的原因，25%的儿童 伴SCA的患者在MRI扫描上有脑梗塞的证据。大多数人 SCA儿童卒中是进展性脑梗塞的结果 颅内大血管变窄，但其背后的病理生理 这些损伤是未知的。在一项初步研究中，我们记录了 人类白细胞抗原(人类白细胞抗原)的特殊表型与 SCA儿童脑梗塞风险增加。的目标是 本研究是为了确认和扩展这一初步研究，通过确定 无论是特定的人类白细胞抗原等位基因还是人类白细胞抗原单倍型都会增加罹患糖尿病的风险 儿童SCA中的脑梗塞。此外，人类白细胞抗原之间的关联 等位基因和梗塞类型(大血管与小血管、静止性与症状性) 将会被探索。将对储存的DNA样本进行分子人类白细胞抗原配型 来自SCA患者，他们之前在两个大的 多机构试验--镰状细胞性贫血的卒中预防试验 (STOP)和镰刀细胞病的合作研究(CSSCD)。所有这些都是 作为这些试验的一部分，患者接受了盲法MRI扫描。 脑部MRI证实的SCA患者的HLA表型频率 脑梗塞将与MRI阴性的SCA患者进行比较 用于治疗脑梗塞。这些发现可能会对患有癌症的儿童产生深远的影响 SCA，因为人类白细胞抗原配型可作为鉴别这些患者的标志物。 中风的风险更高。及早识别这些患者将有助于 对中风高危人群的预防干预和避免 在风险较低的人群中进行潜在的毒性治疗。

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.