Expression Of TLR2,TLR3,TLR4 In Peripheral Blood Monocytes Of Patients With Hemophagocytic Syndrome

Objective: In this study,we analyze the expression of Toll like receptor 2,3,4 and downstream signaling molecules in peripheral blood mononuclear cells of children with hemophagocytic syndrome,and provide a theoretical basis for the diagnosis and treatment of hemophagocytic syndrome.Methods: 18 cases of primary hemophagocytic syndrome and 18 cases of normal healthy children are selected by case control study.TLR2,TLR3 and TLR4 protein expressions are detected by flow cytometry.While Real-time quantitative PCR is used to detect m RNA expression of IL-1?,IFN-?,IFN-?,TNF-? in the TLR pathway and plasma concentrations of which are measured by enzyme-linked immunosorbent assay(ELISA).Results: 1)The expressions of TLR2,3,4 in peripheral blood mononuclear cells of newly diagnosed HLH group are significantly higher than that of healthy control group and the differences were significant(P<0.01).2)There are differences in the expression levels of TLR2,3,4 signaling pathway transduction molecules My D88,TRAF6,IRAK4,TRAM,TRIF,TBK1,IRF3 between thr patient group and the healthy control group,and show that My D88,TRAF6,IRAK4 m RNA expression levels of HLH group are higher than the healthy control group(P<0.01).The differences of expression levels of TRIF,TBK1,IRF3 m RNA were not significant(P>0.05),While the TRAM m RNA expression of patient group is down regulated,which were detected by PT-PCR.3)The levels of IL-1?,IFN-?and TNF-? in plasma of HLH group are significantly higher than those of healthy group(P<0.05).The concentration of IFN-? expression in HLH group are higher than those in control group,but the difference is not significant(P> 0.05).Conclusions: 1)The expressions of TLR2,3,4 in peripheral blood mononuclear cells of HLH patients are significantly increased,which is one of the major reason of HLH.2)The occurrence of HLH may be due to endogenous / exogenous ligand induced TLR2/4-MyD88 dependent signaling pathways and effector molecules,such as IRAK4,are activated and the presence of TRAM,TRIF and other molecules is inhibited by the inactivation or expression of HLH.3)Inflammatory factor storm may be due to the activation of My D88 dependent signaling pathways and the high level of inflammatory cytokines.At the same time,the abnormal expression of TRIF signaling pathway,leading to the release of type I interferon and the ability to clear the virus which caused the imbalance of factor secretion and the stimulation of virus,leading Mass aggregation of inflammatory factors(IL-1?,TNF-?,IFN-?).