Nuclear factor-κB1 and MicroRNA-146a polymorphisms and risk of acute graft versus host disease post allogeneic stem cell transplantation.

Autor: Mossallam GI; Bone Marrow Transplantation Laboratory Unit, National Cancer Institute, Cairo University, Cairo, Egypt. Electronic address: ghada.mossallam@nci.cu.edu.eg., Fattah RA; Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt., Mahmoud HK; Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2020 Mar; Vol. 225 (2), pp. 151876. Date of Electronic Publication: 2019 Nov 27.
DOI: 10.1016/j.imbio.2019.11.011
Abstrakt: Acute graft-versus-host disease (aGVHD) is a severe inflammatory complication of haematopoeitic stem cell transplantation. The nuclear factor- Kappa Beta (NF-κB) signaling pathway regulates T cell activation. The NF-κB controls the expression of microRNA-146a (miR-146a) that in turn regulates NF-κB activation through a negative feedback loop. We aim to analyze the association between NF-κB1 encoding p50 (rs28362491, -94 in.ertion/deletion ATTG) and miR-146a (rs2910164, G > C) polymorphisms and risk of aGVHD. Genotyping was performed for 135 HLA-matched donors using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).The incidence of aGVHD grades II-IV was 24/135 (17.8 %). NF-κB1 genotype and cytomegalovirus infection were significantly associated with risk of aGVHD II-IV (p = 0.022, HR = 3.17, 95 % CI:1.18-8.51 and p = 0.048, HR = 2.56, 95 % CI:1.01-6.52, respectively). In multivariate analysis, NF-κB1homozygous deletion/deletion genotype was the only independent risk factor associated with aGVHD II-IV (p = 0.013, HR = 3.50, 95 % CI:1.30-9.44). No significant association could be observed between miR-146a polymorphism and aGVHD. Combined NF-κB1 and miR146a genotype analysis warrants investigation in a larger cohort. Our preliminary data do not support the association between miR146a and aGVHD, but suggest an association between NF-κB1 and risk of aGVHD that may pave the way for the development of a novel targeted therapy if proved in a larger cohort.
Competing Interests: Declaration of Competing Interest No conflict of interest
(Copyright © 2019. Published by Elsevier GmbH.)
Databáze: MEDLINE
Externí odkaz: