TLR4炎症通路与慢性移植物抗宿主病合并干眼症的相关性

The involvement of Toll-like receptor 4 inflammatory signaling in dry eye associated with cGVHD

目的:探讨Toll样受体4(TLR4)信号通路与慢性移植物抗宿主病(cGVHD)合并干眼症的关系,以揭示炎症反应在该疾病发生发展中的作用。方法:纳入18例诊断为cGVHD合并干眼症的患者,并以18例移植后发生cGVHD但没有合并干眼症患者为对照。采集两组患者的干眼评分、OSDI评分和Schirmer′s实验结果。收集患者外周静脉血并应用实时定量PCR或ELISA的方法检测TLR4、NF-κB、TNF-α的表达水平。结果:cGVHD合并干眼症患者外周血中的TLR4、NF-κB、TNF-α的m RNA水平均较对照组明显升高。相关性分析显示TLR4表达水平与cGVHD合并干眼症的OSDI评分呈正相关和Schirmer′s结果呈负相关。结论:TLR4介导的炎症信号通路参与了cGVHD合并干眼症的发生、发展。

Objective This study aims to investigate whether the TLR4-mediated nuclear factor- kappa B （NF-KB） signaling pathway contributes to the inflammatory process of dry eye associated with chronic graft- versus-disease （cGVHD）. Methods 18 patients diagnosed as dry eye associated with eGVHD based on the clinical presentation and Schirmer＇s test were enrolled in the study, 18 cGVHD patients without dry eye were considered as controls. Peripheral blood was collected and the serum and PBMC were extracted. The expressions of TLR4 and its downstream molecules, NF-κB and tumor necrosis factor （TNF）-α, were measured by quantitative Real- Time PCR （qRT-PCR） or Enzyme-linked Immuno Sorbent Assay （ELISA）. Results TLR4 mRNA in the peripheral blood from patients with dry eye related to cGVHD increased significantly compared with the controls. The levels of NF-κB and TNF-α were also significantly upregulated in these patients. Importantly, the TLR4 level was strongly correlated with the OSDI and the Schirmer＇s test in dry eye related to cGVHD compared with the controls. Conclusions The TLR4-mediated pro-inflammatory signaling pathway is activated in dry eye associated with cGVHD, which may predict the onset and progression of disease.