Graft-versus-host disease (GvHD) represents the main complication after haematopoietic stem cells transplantation (HSCT). Despite the HLA matching between donor (D) and recipient (R), acute GvHD (aGvHD) occurs in 20-40% of HSCT R. In these cases, D/R minor histocompatibility antigens (mHAg) mismatches (MM), cytokine (Cy) polymorphisms and blood levels seem to play the major role. We evaluated retrospectively, in a group of 77 haematological R who underwent HSCT from HLA identical siblings D and 77 controls, the genotype of some Cy and mHAg in order to outline genetic polymorphisms possibly correlated with the transplant clinical course. We analyzed: CD-31 (C/G -125 and A/G -563), HA-1 (H/R allele), IL-1(T/C +3953), IL-10 (G/A -1082, C/T -592 and C/A -819), IL- 1Ra (1-5 alleles) and TNF-(C/A -862, C/T -856 and G/A at position -574, -375, -307, -243, -237). Allele frequencies of all considered genes resulted in Hardy-Weinberg equilibrium. We also showed complete linkage disequilibrium between -592 and -819 IL-10. According to the literature, we observed positive correlation between the presence of: 1) haplotype - 1082G -819C -592C IL-10, 2) -1082G IL-10; 3) IL-1Ra allele 2 (which all correlate with product high levels), and the absence of severe GvHD (X2 test, p<0.05). A contrary trend was suggested for -307A TNF-a (p<0.098). mHAg MM and Cy genotyping conducted on a larger R group, possibly stratifi ed by pre-transplant treatment, could be useful to identify patients with higher risk of aGvHD.
Non-hla genetic polymorphisms and haemopoietic stem cells transplantation
BERTINETTO, FRANCESCA;AMOROSO, Antonio;RENDINE, Sabina;
2005-01-01
Abstract
Graft-versus-host disease (GvHD) represents the main complication after haematopoietic stem cells transplantation (HSCT). Despite the HLA matching between donor (D) and recipient (R), acute GvHD (aGvHD) occurs in 20-40% of HSCT R. In these cases, D/R minor histocompatibility antigens (mHAg) mismatches (MM), cytokine (Cy) polymorphisms and blood levels seem to play the major role. We evaluated retrospectively, in a group of 77 haematological R who underwent HSCT from HLA identical siblings D and 77 controls, the genotype of some Cy and mHAg in order to outline genetic polymorphisms possibly correlated with the transplant clinical course. We analyzed: CD-31 (C/G -125 and A/G -563), HA-1 (H/R allele), IL-1(T/C +3953), IL-10 (G/A -1082, C/T -592 and C/A -819), IL- 1Ra (1-5 alleles) and TNF-(C/A -862, C/T -856 and G/A at position -574, -375, -307, -243, -237). Allele frequencies of all considered genes resulted in Hardy-Weinberg equilibrium. We also showed complete linkage disequilibrium between -592 and -819 IL-10. According to the literature, we observed positive correlation between the presence of: 1) haplotype - 1082G -819C -592C IL-10, 2) -1082G IL-10; 3) IL-1Ra allele 2 (which all correlate with product high levels), and the absence of severe GvHD (X2 test, p<0.05). A contrary trend was suggested for -307A TNF-a (p<0.098). mHAg MM and Cy genotyping conducted on a larger R group, possibly stratifi ed by pre-transplant treatment, could be useful to identify patients with higher risk of aGvHD.
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