Department of Dentistry, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil.
Department of Dentistry, School of Medicine and Public Health, Salvador, Bahia, Brazil.
PLoS One. 2022 Apr 29;17(4):e0267325. doi: 10.1371/journal.pone.0267325. eCollection 2022.
Among the complications observed after allogeneic hematopoietic stem cell transplantation, graft-versus-host disease (GVHD) is the primary cause of post-transplant mortality. The oral cavity is the second most affected organ target in chronic GVHD. Tissue damage results from the upregulation of inflammatory mediators, which play a critical role in the immunopathogenesis of the disease. This case series observational study aims to evaluate the participation of cytokines, chemokines, transcription factors, and heat shock proteins in the pathogenesis of oral GVHD (oGVHD), describing the mRNA expression of 28 genes selected. Peripheral blood mononuclear cells were isolated from six participants with oGVHD and two without GVHD, and relative expression of transcripts with established roles as inflammatory mediators was determined in triplicate using the human RT2 Profiler™ PCR Array. The gene expression levels in the group with oGVHD were mainly up-regulated compared to those without GVHD. PBMC from oGVDH expressed consistently higher IFN-γ, TNF, IL-1β, CCL2, HSP60 (HSPD1) and HSP90 (HSP90B1). These results can provide a basis for developing new molecular diagnostics and targets therapies for the clinical management of oGVHD.
在异基因造血干细胞移植后观察到的并发症中,移植物抗宿主病(GVHD)是移植后死亡的主要原因。口腔是慢性 GVHD 中第二大受影响的靶器官。组织损伤是由炎症介质的上调引起的,炎症介质在疾病的免疫发病机制中起着关键作用。本病例系列观察性研究旨在评估细胞因子、趋化因子、转录因子和热休克蛋白在口腔 GVHD(oGVHD)发病机制中的参与情况,描述了 28 个选定基因的 mRNA 表达情况。从 6 名患有 oGVHD 和 2 名无 GVHD 的参与者中分离外周血单核细胞,并使用人 RT2 Profiler™PCR 阵列重复三次确定具有既定炎症介质作用的转录物的相对表达。与无 GVHD 组相比,oGVHD 组的基因表达水平主要上调。oGVDH 的 PBMC 持续表达更高水平的 IFN-γ、TNF、IL-1β、CCL2、HSP60(HSPD1)和 HSP90(HSP90B1)。这些结果可为开发新的分子诊断和靶向治疗 oGVHD 的临床管理提供依据。