HLA DRB1 alleles, IFN-γ and TGF-β 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-γ and TGF-β 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-β and IFN-γ 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-β TC genotype was found with a higher rate in the patient group (p=0.031). Association of the DRB1*04 allele with the IFN-γ 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-γ CT was found to have a protective role in occurrence of aGvHD (p=0.044). Association of the DRB1*15 allele with IFN-γ TT was found with a higher rate in a GvHD (p=0.050). Conclusions It is thought that polymorphism of HLA-DR15 and IFN-γ CC may contribute to the development of c-ALL, while IFN-γ CT might be protective for aGvHD.

Human Leukocyte Antigen Alleles (HLA-A, HLA-B, and HLA-DRB1) are associated with Acute Lymphoblastic Leukemia (ALL) : A Case-Control Study in a Sample of Iranian Population

“…Research in Turkey highlighted several alleles such as A03 and DRB104 as predisposing factors, with the DRB104 allele specifically linked to an increased risk of ALL, in contrast to the standard risk associated with the DRB107 allele [3]. More recent findings suggest that the MBL2 BB genotype, when combined with DRB107 or co-inherited with HLA-DRB104 and DRB107, could contribute to pediatric ALL, emphasizing the role of initial immune defense mechanisms [2].…”

“…

Acute lymphoblastic leukemia (ALL), the most prevalent cancer among children, sees about 75% of leukemia cases globally [1,2]. Despite high survival rates exceeding 85% for those without relapse, those experiencing relapse face severe prognoses.

…”