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Post-Transplant Events

KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12 HLA matched, hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 44, pages 97–103 (2009)Cite this article

Abstract

Interactions of polymorphic killer Ig-like receptor (KIR) receptors with KIR ligands have been shown to modify the outcome of hematopoietic SCT (HSCT). The association of these genetic factors with different transplantation endpoints, however, varies substantially, depending on clinical and study setup variables. We aimed to assess whether KIR ligands, KIR genes and KIR haplotypes are associated with HSCT outcome of 124 patients with various hematological malignancies, transplanted with 12/12 HLA matched grafts from unrelated donors. For this purpose, patient and donor KIR gene and KIR ligand polymorphisms were determined and correlated with clinical data in simple and multiple models. We found that a missing HLA-C2 ligand for donor inhibitory KIR2DL1 was significantly associated with an increased risk of acute GVHD (aGVHD) (II–IV) (hazard ratio (HR)=2.23, 95% confidence interval (95% CI): 1.21–4.10, P=0.010), as were the AA KIR haplotypes in patients and donors in HLA-C1CX (HR=2.37, 95% CI: 1.16–4.84, P=0.018) and in HLA-Bw4− (HR=3.20, 95% CI: 1.35–7.60, P=0.008) patients. On the contrary, transplantation of HLA-C1C2 patients with KIR2DS2 positive grafts were associated with a decreased risk of aGVHD (II–IV) (HR=0.24, 95% CI: 0.07–0.85, P=0.027). Thus, our single center study provides evidence for the modification of aGVHD risk by KIRs and their ligands.

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Acknowledgements

We thank Dejan Stokic at the Complex System Research Group, ENT, Medical University of Vienna, for his help with the KIR genotype database. This work was supported in part by the European Commission Grant MCRTN-CT-2004-512253 (TRANSNET).

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Authors and Affiliations

  1. Division of Blood Group Serology, Medical University of Vienna, Vienna, Austria

    K Ludajic, A Rosenmayr, I Fae & G F Fischer

  2. Department of Genetic Epidemiology, University of Goettingen, Goettingen, Germany,

    Y Balavarca & H Bickeböller

  3. Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria

    M Kouba, D Pohlreich, P Kalhs & H T Greinix

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  1. K Ludajic
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Correspondence to G F Fischer.

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Ludajic, K., Balavarca, Y., Bickeböller, H. et al. KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12 HLA matched, hematopoietic stem cell transplantation. Bone Marrow Transplant 44, 97–103 (2009). https://doi.org/10.1038/bmt.2008.432

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