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Graft-Versus-Host Disease

The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 45, pages 1435–1441 (2010)Cite this article

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Abstract

The role of killer Ig-like receptors (KIR) in SCT was analyzed. A total of 75 Chinese patients were transplanted with T-depleted hematopoietic stem cells from unrelated donors. Among the 75 donor–recipient pairs, 60 were HLA 10/10 matched and 15 had some mismatches at HLA-C. Transplants from KIR haplotype B/x group donors showed significantly higher overall survival rates compared with those from KIR haplotype A/A donors (relative risk (RR) 3.1 (95% confidence interval (CI) 1.1–8.6), P=0.007). In the haplotype A/A group, a higher risk of acute GVHD (aGVHD) (RR 9.0 (95% CI 1.2–66.9), P=0.01), especially grade III–IV aGVHD (P=0.006), was observed when the donor was homozygous for the full-length expressed KIR2DS4*00101 allele. Real-time PCR showed that a high expression of inhibitory KIR (2DL1 and 3DL1) in the early stages (<90 days) after transplantation correlated with the development of aGVHD (z=2.558, P=0.011). Our findings indicated a significant association of full-length KIR2DS4 or KIR2DL1/3DL1 expression with the occurrence of aGVHD. In aggregate these results suggested that combining KIR and HLA genotyping could help in the selection of transplant donors and improve the outcome of transplantation. Dynamic detection of KIR2DL1/3DL1 expression would be beneficial for prediction of aGVHD after transplantation.

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Acknowledgements

The KIR2DS4 sequencing was supported by a grant to Drs Carolyn Hurley and Jennifer Ng (CW Bill Young Marrow Donor Recruitment and Research Program, Georgetown University Medical Center). We thank them for their support of this project. We thank Prof Yueping Shen (Medical College of Soochow University) for his help in statistical analysis. This work was supported by the grants from The Science Foundation of Department of Health (No: wkj2006-2-023); The Talent Man Foundation of Jiangsu Province (No: 07-B-21); Natural Science Foundation of Jiangsu Province (No: 07kj320106); and The Cooperation Foundation of International (No: SWH0716).

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Authors and Affiliations

  1. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Jiangsu, China

    X J Bao, A N Sun, Q C Qiu, X N Yuan, Z X Chen & J He

  2. Department of Pediatric, CW Bill Young Marrow Donor Recruitment and Research Program, Georgetown University Medical Center, Washington, DC, USA

    L H Hou & M H Chen

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  1. X J Bao
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Bao, X., Hou, L., Sun, A. et al. The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT. Bone Marrow Transplant 45, 1435–1441 (2010). https://doi.org/10.1038/bmt.2009.357

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