IL10 Polymorphism Linked To Improved Outcomes After Stem-Cell Transplantation

NEW YORK (Reuters Health) - A polymorphism in the promoter region of the interleukin-10 (IL10) gene is associated with a decreased risk of graft-versus-host disease and improved survival after hematopoietic stem-cell transplantation, new research indicates.

Cytokines and other immune regulators are thought to play a key role in the pathogenesis of GVHD. In the current study, Dr. John A. Hansen, from Fred Hutchinson Cancer Research Center in Seattle, and colleagues looked at polymorphisms in several cytokine genes and found a link between an IL10 variant and outcomes after hematopoietic cell transplantation.

The study, which is reported in the December 4th issue of The New England Journal of Medicine, involved 570 transplant recipients in the initial gene analysis phase and a separate group of 423 recipients in the verification phase. All of the subjects had received their cells from an HLA-identical sibling.

Subjects who were homozygous for the variant IL10 -592A allele were 60% less likely to develop grade III or IV GVHD than subjects homozygous for the regular allele. Subjects with only one copy of the variant allele exhibited a risk reduction of 30%.

Homozygosity for the variant allele was also associated with 40% reduction in the risk of death in remission compared with homozygosity for the regular allele. In contrast, heterozygosity for the variant allele did not seem to reduce this risk.

The researchers believe that beneficial effects associated with the polymorphism may relate to increased production of IL10. "We hypothesize that a high level of interleukin-10 production by recipients' cells during the early post-transplantation period mitigates the intensity of the alloimmune response and GVHD-induced inflammation, thereby reducing the clinical manifestations of GVHD and associated mortality."

Although verification in "additional patients is always desirable, we believe that the data already support the inclusion of the IL10 genotype in the standard evaluation of a patient who is under consideration for transplantation" of stem cells from an HLA-identical sibling donor, Dr. Kenneth R. Cooke and Dr. James L. M. Ferrara note in a related editorial.

In addition to improving risk assessment, knowledge of the IL10 genotype "is likely to influence the choice of an immunosuppressive-drug regimen and the rate at which the drugs are tapered," the editorialists, from the University of Michigan at Ann Arbor, write.

Source: N Engl J Med 2003;349:2183-2184,2201-2210. [ Google search on this article ]

MeSH Headings: Polymorphism, Single Nucleotide

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