Relative of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation

N ENGL J MED, Vol 349(2003), p2201-2210

Speaker：林長儀

Commentator：李伯璋  醫師             Date：2004/06/02  13:00~14:00

Abstract：

  Hematopoietic cell transplantation (HCT) is an effective therapy in helping patients to reestablish their marrow and immune functions; however, HCT becomes a potential toxic therapy when the donor possesses different genetic background from the recipient. The most common implication is graft-versus-host disease (GVHD) that occurs despite immunosuppressive prophylaxis. Besides the interaction between antigen-present-cells of the recipient and mature T cells of the donor, the pathogenesis of GVHD also depends on cytokines and other regulators of the immune response（e.g. IL-1β、IL-1RA、IL-6、IL-10、TNF-α）¹. Previous studies show that a single-nucleotide-polymorphism (SNP) in a gene may affect the transcription or translation of the genes or the secretion or function of the corresponding proteins². In this study, Authors try to screen SNPs in several cytokine genes to find out the relationship between the SNPs and GVHD. The results show that the recipient’s IL-10 promoter region genotype is significantly associated with the risk of acute GVHD in 570 HLA-A2 patients. Analysis of SNPs in IL-10 promoter with 993 patients show that the IL-10 -592A/A genotype is associated with a lower risk of acute GVHD (p=0.02) and death in remission (p=0.05), as has compared with -592C/C genotype. Furthermore, the haplotype analysis of IL-10 promoter show that A-T-A (-1082/-819/-592) haplotype performs a lower risk of acute GVHD than A-C-C or G-C-C haplotype. The data suggest that IL-10 -592 polymorphism has a dominant effect on the outcome of HCT. Further ongoing researches could prompt new approaches to reduce the toxicity of GVHD.

References：

1.          Krenger, W., G. R. Hill, and J. L. M. Ferrara. 1997. Cytokine Cascades in Acute Graft-versus-Host Disease. Transplantation. 64:553-8.

2.          Bidwell, J., et al.. 1999. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun. 1:3-19.