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.
| Hoppe, Carolyn; Klitz, William; D'Harlingue, Katherine et al. (2007) Confirmation of an association between the TNF(-308) promoter polymorphism and stroke risk in children with sickle cell anemia. Stroke 38:2241-6 |
| Hoppe, Carolyn; Klitz, William; Cheng, Suzanne et al. (2004) Gene interactions and stroke risk in children with sickle cell anemia. Blood 103:2391-6 |
| Hoppe, Carolyn; Klitz, William; Noble, Janelle et al. (2003) Distinct HLA associations by stroke subtype in children with sickle cell anemia. Blood 101:2865-9 |
