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Significance of CTLA-4 and CD14 genetic polymorphisms in clinical outcome after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 40, pages 1001–1002 (2007)Cite this article

In addition to the genes involved in the ‘HLA barrier’ in solid organ and hematopoietic stem cell transplantation (HSCT), and to the polymorphisms of the KIR family genes of natural killer cell receptors, there has been growing attention in the past few years regarding the role of other gene polymorphisms of molecules potentially involved in immune reactions following HSCT.1 In particular, attention has been paid to the sequence polymorphisms of cytokine and cytokine gene receptor genes, as these molecules are involved in the modulation of host response to tissue injury and inflammation, with the ensuing activation of donor competent cells2 (for a recent extensive review, please refer to Petersdorf1). Beyond the events linked to the T-cell receptor activation that follows the binding of T cell to HLA molecule–peptide complex, the balance between T-cell activation and inactivation is dependent on a system of antigen-independent signaling molecules, the B7(CD80/CD86)/CD28 interaction pathway. The cytotoxic T-cell CTLA-4 antigen is highly homologous with regard to CD28, and competes for B7 binding, resulting overall in downregulation of T-cell response; thus, CTLA-4 supposedly plays a key role in tolerance regulation.3 The association of some CTLA-4 gene polymorphisms, possibly causing a reduction of mRNA and protein levels, with a variety of autoimmune disorders, has been previously reported.4

Recently, Perez-Garcia et al.5 reported that the clinical outcomes of recipients of HLA-identical allogeneic stem cell transplantation from a sibling donor could be predicted by the analysis of CTLA-4 polymorphism. They studied two common CTLA-4 polymorphisms in 536 HLA-identical sibling donors for allogeneic HSCT and found that the donor CT60 polymorphism reduced overall survival (hazard ratio (HR), 3.80), due to higher incidence of relapse (HR, 1.71), when at least one G allele was present, and increased the development of acute GVHD (HR, 1.54) in the presence of the AA genotype.

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Acknowledgements

This work was supported by grants from MIUR no. 2004068284_002 and ADMO, Florence.

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Authors and Affiliations

  1. Department of Hematology, University of Florence, Florence, Italy

    A M Vannucchi, S Guidi, P Guglielmelli, S Glinz, L Lombardini & A Bosi

  2. Bone Marrow Transplant Centre, San Giovanni Battista Hospital, Turin, Italy

    A Busca & F Locatelli

  3. Transplantation Immunology Service, San Giovanni Battista Hospital, Turin, Italy

    A M Dall'Omo

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  1. A M Vannucchi
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Correspondence to A M Vannucchi.

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Vannucchi, A., Guidi, S., Guglielmelli, P. et al. Significance of CTLA-4 and CD14 genetic polymorphisms in clinical outcome after allogeneic stem cell transplantation. Bone Marrow Transplant 40, 1001–1002 (2007). https://doi.org/10.1038/sj.bmt.1705850

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