Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants.

摘要: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is strongly implicated in graft-versus-host disease (GVHD) and other acute bone marrow transplant (BMT) complications. antiinflammatory interleukin-10 (IL-10) antagonizes TNF-alpha reduces GVHD. We previously showed association of recipient TNF (TNFd) IL-10 (IL-10(-1064)) gene polymorphisms with GVHD severity matched sibling BMT using only cyclosporin A monotherapy. current study tested TNFd IL-10(-1064/-1082) a large cohort (144 donor/recipient pairs) given both cyclosporine (CyA) methotrexate (MTX) prophylaxis. Genotype results were correlated chronic mortality. Patients homozygous for the microsatellite allele 3 had higher early mortality: 23.7% TNFd3/d3 homozygotes died before day 30, compared 6.80% non-d3/d3 recipients (P =.013). Recipients possessing longer IL-10(-1064) alleles developed more severe GVHD: 22.3% 12 to 15 grade III IV GVHD, versus 3.92% those smaller <.01). Other or donor genotypes did not significantly affect conclude that associate mortality dual This supports hypothesis genetic predisposition towards complications than histocompatibility antigen disparity.