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Graft-Versus-Host Disease

Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation

Bone Marrow Transplantation volume 41, pages 821–826 (2008)Cite this article

Abstract

Polymorphisms in cytokine genes can influence immune responses and inflammation and thereby affecting the outcome of hematopoietic stem-cell transplantation. We analyzed a single-nucleotide polymorphism in the gene for the interleukin-23 receptor (IL-23R) (1142G>A) in a cohort of 221 transplant recipients and their human leukocyte antigen (HLA)-identical sibling donors and in a second cohort of 186 transplant recipients and their HLA-identical unrelated donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariate analysis. The donor's IL-23R genotype was significantly associated with a reduced risk of acute GVHD in both cohorts for patients after transplant. Analysis of all 407 transplant recipients showed that IL-23R (1142G>A, Arg381Gln) genotype of the donor was associated with a decreased risk of grades 2–4 acute GVHD (31.6 compared to 51.0%, P=0.02) and grades 3–4 severe acute GVHD (3.9 compared to 23.4%, P=0.003). Death in remission was significantly lower in patients transplanted from donors with variant IL23-R (11.7 versus 27.7%, P=0.028), whereas overall survival or relapse rates were not influenced significantly by the IL-23R genotype. Among recipients of hematopoietic cells from HLA-identical donors, the IL-23R (Arg381Gln) gene variant on the donor side has a protective effect on the occurrence of acute GVHD in recipients after transplantation.

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Acknowledgements

We would like to thank Silke Gottwald, Christiane Schary, Melanie Kroll and Ines Riepenhoff (all Essen, Germany) for their excellent technical assistance with genotyping analyses. This work was supported by grants from the Josè Carreras Stiftung and Kulturstiftung Essen (05 032 Elmaagacli).

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany

    A H Elmaagacli, M Koldehoff & D W Beelen

  2. TIB MOLBIOL Syntheselabor GmbH, Berlin, Germany

    O Landt

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  1. A H Elmaagacli
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  2. M Koldehoff
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  3. O Landt
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  4. D W Beelen
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Correspondence to A H Elmaagacli.

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Elmaagacli, A., Koldehoff, M., Landt, O. et al. Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation. Bone Marrow Transplant 41, 821–826 (2008). https://doi.org/10.1038/sj.bmt.1705980

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