Role of non-HLA genetic polymorphisms in graft-versus-host disease after haematopoietic stem cell transplantation

Int J Immunogenet. 2006 Oct;33(5):375-84. doi: 10.1111/j.1744-313X.2006.00630.x.

Abstract

Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / genetics*
  • Gene Frequency
  • Graft vs Host Disease / genetics*
  • HLA Antigens / genetics
  • Haplotypes
  • Hematologic Diseases / therapy
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-10 / genetics
  • Living Donors
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Cytokines
  • HLA Antigens
  • Interleukin-1
  • Interleukin-10