Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Oral Dis. 2012 Nov;18(8):816-22. doi: 10.1111/j.1601-0825.2012.01955.x. Epub 2012 Jul 3.
Graft-versus-host disease is a major complication after allogenic hematopoietic stem cell transplantation. Interferon gamma is an important pro-inflammatory cytokine involved in this disease. Cytokine gene polymorphisms are associated with functional differences in cytokine expression and can alter the clinical course of graft-versus-host disease. This study aimed to investigate the association between IFN-γ levels in saliva, blood, and IFNG polymorphisms, as well as the occurrence of acute graft-versus-host disease in allogenic HSCT.
Fifty-eight consecutive allogenic hematopoietic stem cell transplantation recipients and their donors were prospectively studied. IFN-g levels in saliva and blood were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allogenic HSCT (day +100) or until death. Saliva and/or blood samples were obtained from the recipients and donors to determine IFNG gene polymorphisms.
Increased saliva and blood IFN-g levels were observed in patients that had developed aGVHD. In the saliva, the peak levels of IFN-g could be found one week before aGVHD diagnosis, while in the blood, peak levels of IFN-g could be only observed upon diagnosis. A significant association could be identified between the recipients'IFNG genotypes and the IFN-g levels in their blood, at +14 days after HSCT. No association could be observed between IFNG gene polymorphisms and the aGVHD.
The present study shows that the genetic background of recipients can influence the production of IFN-g. Moreover, as IFN-g levels in the saliva and blood were found to be associated with aGVHD development, this cytokine may be a useful predictor of acute graft-versus-host disease.
移植物抗宿主病是异基因造血干细胞移植后的主要并发症。干扰素γ(IFN-γ)是一种重要的促炎细胞因子,参与该病的发生。细胞因子基因多态性与细胞因子表达的功能差异有关,并可能改变移植物抗宿主病的临床病程。本研究旨在探讨唾液、血液中 IFN-γ水平与 IFNG 多态性以及异基因 HSCT 中急性移植物抗宿主病发生的关系。
前瞻性研究了 58 例连续异基因造血干细胞移植受者及其供者。采用 ELISA 法检测唾液和血液中的 IFN-γ水平。从移植前 7 天(-7 天)至异基因 HSCT 后 100 天(+100 天)或直至死亡,每周采集受者的唾液和/或血液样本,以评估 IFN-γ水平。采集受者和供者的唾液和/或血液样本,以确定 IFNG 基因多态性。
发生急性移植物抗宿主病的患者唾液和血液 IFN-γ水平升高。在唾液中,IFN-γ的峰值水平可在发生急性移植物抗宿主病前一周发现,而在血液中,IFN-γ的峰值水平仅在诊断时出现。HSCT 后第 14 天,受者 IFNG 基因型与血液 IFN-γ水平之间存在显著相关性。未观察到 IFNG 基因多态性与急性移植物抗宿主病之间的相关性。
本研究表明,受者的遗传背景可能影响 IFN-γ的产生。此外,由于唾液和血液中 IFN-γ水平与急性移植物抗宿主病的发生相关,因此该细胞因子可能是急性移植物抗宿主病的有用预测因子。