Abstract
CTLA-4 is a negative regulator of activated T cells and the association of CTLA-4 polymorphisms with autoimmune diseases and transplant outcome has been reported. We evaluated the effect of donor CTLA-4 polymorphisms on outcome after allogeneic hematopoietic SCT (HSCT). We analyzed 147 Japanese HLA-matched sibling recipients and their donors who had undergone allogeneic HSCT. Genotyping of three single-nucleotide polymorphisms in CTLA-4 (−318, +49, CT60) was performed using TaqMan-PCR. According to the international HapMap database, only these three CTLA-4 haplotypes, classified as C-G-G, C-A-A and T-A-G, are present in the Japanese population. In this study, percentage expression of the C-G-G, C-A-A and T-A-G haplotypes was 59.5, 30.6 and 9.9%, respectively. Recipients of the C-A-A haplotype donor showed a significantly lower risk of relapse (HR: 0.54, 95% CI: 0.30–0.97, P=0.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36–1.0, P=0.054) than did recipients of a donor without the C-A-A haplotype. The presence or absence of the C-A-A haplotype did not affect GVHD or non-relapse mortality. As the presence of the C-A-A haplotype reduced relapse risk and improved survival after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for donor selection.
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Acknowledgements
This study was supported in part by a Grant-in-Aid for Scientific Research (20890096) from Japan Society for the Promotion of Science, and a Health and Labour Science Research Grant (Research on Human Genome and Tissue Engineering) from the Ministry of Health, Labour and Welfare of Japan.
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Murase, M., Nishida, T., Onizuka, M. et al. Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT. Bone Marrow Transplant 46, 1444–1449 (2011). https://doi.org/10.1038/bmt.2010.319
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DOI: https://doi.org/10.1038/bmt.2010.319
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