HLA gene polymorphism and susceptibility for stroke in children with sickle cell anemia

ABSTRACT

Stroke occurs in 8-10% of children with Sickle Cell anemia [SCA] and is a major cause of morbidity. Prevention of first stroke would be preferable because even one stroke can cause irreversible brain injury. The association of HLA type with stroke provides the first evidence of a multigenic involvement in a specific manifestation of SCA. We investigated eleven children with SCA with magnetic resonance imaging [MRI] abnormalities consistent with cerebral infarcts [group I] and fourteen asymptomatic children with SCA with normal MRI scans [group II] to determine whether HLA type was associated with risk of stroke with SCA. Comparison, of the results of HLA typing between the SCA patients with a positive and those with a negative MRI revealed significant difference in distribution of alleles at the class II loci. For DRB1, the DR3 alleles, DRB1*0301and*0302 appeared to be associated with susceptibility to stroke. The DR15 alleles, DRB1* 1501 and 1503, were protective for stroke. For the DQB1 locus, DQB1 0201 was associated with stroke, while DQB1*0602 appeared protective. Documentation of an association between HLA alleles and risk of stroke in patients with SCA suggests that HLA system plays a role in the pathophysiology of vascular changes leading to stroke