Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3562-3567
Evidence for HLA-related susceptibility for stroke in children
with sickle cell disease
Lori A. Styles,
Carolyn Hoppe,
William Klitz,
Elliott Vichinsky,
Bertram Lubin, and
Elizabeth Trachtenberg
From the Department of Hematology/Oncology, Children's Hospital
Oakland, Oakland, CA; School of Public Health, University of
California, Berkeley, CA; Children's Hospital Oakland Research
Institute, Oakland, CA.
Cerebral infarction occurs in one quarter of all children with
sickle cell anemia (SCA). There is an increased risk of stroke in
siblings with SCA, suggesting genetic factors may influence risk of
stroke. The authors investigated whether HLA type was associated with
risk of stroke in children with SCA. Fifty-three patients with SCA
underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA
class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic
resonance imagining (MRI)-documented evidence of cerebral infarction,
and the remaining 31 patients had negative MRI scans. Comparison of the
results of HLA typing between the SCA patients with a positive and
those with a negative MRI documented that the 2 groups differed with
respect to the class I HLA-B (P = .012), and the class II
HLA-DRB1 (P = .0008) and DQB1 (P = .029).
Susceptibility associations at the HLA-DRB1 locus included both DR3
alleles, where DRB1*0301 and *0302 were both associated with an
increased risk of stroke. Protective associations were found in the DR2
group, where DRB1*1501 was protective for stroke. DQB1*0201, which is
in linkage disequilibrium with DRB1*0301, was also associated with
stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501,
was protective. Specific HLA alleles may influence the risk of stroke
in children with SCA. HLA typing may prove useful in identifying SCA
patients at higher risk for stroke.
