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Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Cellular & Molecular Immunology volume 8, pages 276–280 (2011)Cite this article

Abstract

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III–IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)=0.20, 95% confidence interval (CI): 0.06–0.67) in comparison with patients with other IL-10 haplotypes (P=0.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR=0.17, 95% CI: 0.012–0.320) versus other IL-10 haplotypes (P=0.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P=0.02, HR=0.21, 95% CI: 0.05–0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

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Authors and Affiliations

  1. Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece

    Evgenios Goussetis, Ioulia Peristeri, Vasiliki Kitra, Anna Paisiou, Sofia Karatasaki, Alexandra Soldatou & Stelios Graphakos

  2. Immunology Department, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece

    Ioanna Varela, Kleopatra Spanou, Olga Moraloglou & Nikki Constantinidou

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  1. Evgenios Goussetis
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  2. Ioanna Varela
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Correspondence to Evgenios Goussetis.

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Goussetis, E., Varela, I., Peristeri, I. et al. Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience. Cell Mol Immunol 8, 276–280 (2011). https://doi.org/10.1038/cmi.2011.4

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