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Identification of a specific HLA class II haplotype strongly associated
with susceptibility to cyclosporine-dependent aplastic anemia
S Nakao, H Takamatsu, T Chuhjo, M Ueda, S Shiobara, T Matsuda, T Kaneshige and H Mizoguchi
Third Department of Medicine, Kanazawa University School of Medicine,
Japan.
Hematopoietic function of some aplastic anemia (AA) patients is dependent
on the administration of cyclosporine (CyA). To investigate whether certain
HLA class II genes are associated with susceptibility to such CyA-dependent
AA, we determined the HLA class II alleles of 59 AA patients treated with
CyA. Among 26 patients successfully treated with CyA, 13 required a small
dose of CyA to maintain stable hematopoiesis. Of these 13 AA patients, 10
shared an HLA class II haplotype of DRB1*1501-DQA1*0102-DQB1*0602. None of
the 13 responders who obtained a sustained remission off CyA therapy
possessed this haplotype. In the 10 patients who shared the HLA class II
haplotype, single-strand conformation polymorphism analysis of each gene
fragment of this haplotype failed to detect a polymorphism in the
nucleotide sequence. When the AA patients were assessed for their
likelihood to respond to CyA therapy, the response rate in patients with
this haplotype (71%) was significantly higher than that of patients with
another haplotype associated with HLA-DR2, DRB1*1502-DQA1*0103- DQB1*0601
(36%) and that of patients without HLA-DR2 (35%). These findings indicate
that the CyA-dependent response of AA is closely related to an HLA class II
haplotype of DRB1*1501-DQA1*0102-DQB1*0602 and suggest that, in AA patients
with this haplotype, immune mechanisms play an important role in the
pathogenesis of bone marrow failure.
Volume 84,
Issue 12,
pp. 4257-4261,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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