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.

İnsan Lökosit Antijeni (HLA) ekspresyon seviyelerinin, UTR bölgelerindeki (untranslated region) tek nükleotid polimorfizmleri (SNP) tarafından genetik olarak kontrol edildiği düşünülmekte olup, ekspresyon varyantları hematopoietik kök hücre nakli (HKHN) başarısı ile ilişkilendirilmiştir. Akraba dışı donör taramasında genel olarak kabul edilen uyum oranı yüksek çözünürlükte HLA-A, -B, -C, -DRB1 ve -DQB1 lokusu seviyesinde iken son zamanlarda yürütülen çalışmalar, HLA-DPB1 lokusu için hasta ve donör arasında mevcut olan uyumsuzlukların alloreaktif T-hücre yanıtlarını indükleyebileceğini ve allojeneik hematopoietik kök hücre nakli (AHKHN) sonrası akut graft versus host hastalığı (aGvHH) gelişimi ve genel sağ kalım üzerinde etkili olabileceğini göstermiştir. HLA-DPB1 uyumsuzluklarının T hücre epitop (TCE) gruplarına dayalı olarak sınıflandırılmasının, AHKHN'den sonra tolere edilebilecek (permissive) ve tolere edilmeyen yani riskleri artıracak (non-permissive) uyumsuzlukları TIP BİLİŞİMİ

No abstract

No abstract

Objectives Sequence variants in cytokine genes are related to affect cytokine gene levels. In this study, it was aimed to examine eight single nucleotide polymorphisms (SNPs) in five cytokine genes (TNF-α, INF-γ, IL-6, IL10, TGF-β) for the Turkish population living in Marmara region and to reveal the genetic distance between the study group and other populations. Methods In this study, three-hundred unrelated healthy individuals were involved and all genotyping were performed by using sequence-specific primers PCR (PCR-SSP) method. The SNP data were analyzed for Hardy Weinberg equilibrium fit by calculating expected genotype frequencies and comparing them to the observed values using Arlequin software version 3.1. The genetic distances between the study group and other populations were calculated and a neighbor-joining tree was constructed by PHYLIP. Results The observed genotypes of TNF-α (−308), IFN-γ (+874), TGF-β (codon 10), and TGF-β (codon 25) of the subjects were found to be similar with other populations investigated in this study. However, there is a significant frequency difference for IL-6 and IL-10 genotypes between populations. Conclusions The current population study provided more reference values for these polymorphisms and generated a control group to be used in further association studies especially for transplantation, GVHD, autoimmune and malign disease.