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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2791.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2865-2869
RED CELLS
Distinct HLA associations by stroke subtype in children with
sickle cell anemia
Carolyn Hoppe,
William Klitz,
Janelle Noble,
Lara Vigil,
Elliott Vichinsky, and
Lori Styles
From the Department of Hematology/Oncology, Children's
Hospital Oakland; and Children's Hospital Oakland Research Institute,
CA.
Children with sickle cell anemia (SCA) carry a 200-fold increased
risk for cerebral infarction. Stroke can be the result of small-vessel
(SV) or large-vessel (LV) disease. However, it is unknown whether these
subtypes result from the same pathophysiologic processes. Complete HLA
genotyping was performed on 231 eligible children previously enrolled
in the Cooperative Study of Sickle Cell Disease (CSSCD). Cerebral
infarction on magnetic resonance imaging (MRI) was documented in 71 patients, and 160 patients had negative findings on MRI. Based on
MRI/magnetic resonance angiography (MRA) findings, infarct
size, and location, 36 patients were classified as having LV stroke and
35 as having SV stroke. When comparing the total MRI+ group with the
MRI group, HLA DPB1*0401 was associated with increased stroke risk
(P = .01), whereas DPB1*1701 (P = .02)
conferred protection from stroke. These DPB1 associations with stroke
were attributed to the SV stroke group, in whom DPB1*0401 was
associated with susceptibility (P = .003) and
DPB1*1701 with protection from stroke (P = .06). In the
LV stroke subgroup, HLA-A*0102 (P = .02) and -A*2612
(P = .007) conferred susceptibility, whereas -A*3301(P = .04) protected from stroke. These results
suggest that specific HLA alleles influence stroke risk and appear to contribute differently to SV and LV stroke subtypes. The distinct HLA
associations with SV and LV stroke suggest that different pathologic
processes may be involved in the development of stroke in children with
SCA. If these results are confirmed in a larger study, HLA type may
serve as a useful marker for the early identification of SCA patients
at high risk for stroke.
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