Role of non-HLA genetic polymorphisms in graft-versus-host disease after haematopoietic stem cell transplantation.
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.
Bertinetto
F E
FE
Transplantation Immunology Service, San Giovanni Battista Hospital, Turin, Italy.
Dall'Omo
A M
AM
Mazzola
G A
GA
Rendine
S
S
Berrino
M
M
Bertola
L
L
Magistroni
P
P
Caropreso
P
P
Falda
M
M
Locatelli
F
F
Busca
A
A
Amoroso
A
A
D000328:Adult; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006402:Hematologic Diseases / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D019520:Living Donors; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D016207:Cytokines; D006680:HLA Antigens; D007375:Interleukin-1; D016753:Interleukin-10