HLA DRB1 alleles, IFN-gamma and TGF-beta Gene Variants in childhood ALL patients

Abstract

Objectives Graft-versus-host disease (GvHD) is a complex clinical syndrome with organ dysfunction as a consequence of a severe immunological reaction mediated by mainly T cells after hematopoietic stem cell transplantation. Our aim is to evaluate the association of HLA-DRB1 alleles, IFN-gamma and TGF-beta gene variations, with childhood ALL (c-ALL) patients and with GvHD after transplantation. Methods This study included 30 high-risk c-ALL patients and 100 controls. HLA-DRB1 alleles were studied by the NGS method, and TGF-beta and IFN-gamma variations were studied by the PCR-RFLP method. Results The rates of HLA-DRB1*15 alleles and IFN-gamma CC genotype were significantly higher in c-ALL patients (p=0.004, p=0.036 respectively). Association of the HLA-DRB1*15 alleles with the TGF-beta TC genotype was found with a higher rate in the patient group (p=0.031). Association of the DRB1*04 allele with the IFN-gamma CC genotype was found with a higher rate in the patient group (p=0.028). Acute GvHD developed in eight of 19 patients who underwent transplantation. IFN-gamma CT was found to have a protective role in occurrence of aGvHD (p=0.044). Association of the DRB1*15 allele with IFN-gamma TT was found with a higher rate in a GvHD (p=0.050). Conclusions It is thought that polymorphism of HLA-DR15 and IFN-gamma CC may contribute to the development of c-ALL, while IFN-gamma CT might be protective for aGvHD.