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

Summary 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.