The Expression And Significance Of MicroRNA In The Plasma Of Patients With Hemophagocytic Lymphohistiocytosis

Objective:In this study,through screening the differential miRNA expression profiles in the plasma of patients with hemophagocytic lymphohistiocytosis(HLH),we aims to search for the miRNAs related to the occurrence of HLH disease,to analyze the correlation between miRNAs expression and clinical laboratory indicators,and to preliminarily explored the role of aberrantly expressed miRNAs in the pathogenesis of HLH。 Method:The plasma of 28 patients who were first diagnosed with HLH in the Department of Hematology,the First Affiliated Hospital of Nanchang University from January 2017 to February 2019 was collected.All patients met the diagnostic criteria of the HLH-2004 guidelines.Plasma of 15 healthy subjects were collected,whose gender and age were matched with those of HLH patients.Gene chip technology was used to detect and screen the differentially expressed miRNA in plasma,and the expression levels of miR-125a-3p and miR-320 a in plasma were detected by real-time PCR.The SPSS software was used to analyze the correlation between miR-125a-3p and miR-320 a expression levels and clinical indicators.The receiver operating charact-eristic curve(ROC curve)was used to evaluate the diagnostic value of miR-125a-3p and miR-320 a for HLH.Result:1.28 patients with HLH manifested with fever,splenomegaly and elevated serum ferritin.64.29% of patients had hemophagocytosis,and patients with complete cytopenia accounted for 96.43%.Only 35.71% of patients manifested with low fibrinogen.In patients with hypertension,sCD25 is elevated by approximately 82.14%.There was no difference in age and gender between the HLH patients and the control group(P=0.399).2.The results of gene chip screening showed that there were 24 differentially expressed miRNAs in the plasma of HLH patients,compared with normal subjects,of which 20 miRNAs were significantly up-regulated and 4 miRNAs were downregulated significantly.3.The expression levels of plasma miR-125a-3p in the HLH group and control group were 7.21±1.48 and 1.53±0.34,respectively.Compared with healthy subjects,the expression of plasma miR-125a-3p of HLH patients was up-regulated,with significant statistical significance(P(27)0.001);the expression level of plasma miR-320 a of HLH patients was significantly higher than that of healthy subjects,the difference was statistically significant(5.83±1.59 and 1.33±0.31,P(27)0.001).4.The correlation analysis between the expression level of plasma miRNA-125a-3p and clinical data of HLH patients showed that the expression of miRNA-125a-3p was not significantly correlated with gender,age,hemophagy,Fbg and sCD25,while was negatively correlated with the laboratory parameters WBC and ANC,and the correlation coefficients were(r(28)-0.463,p(28)0.013)and(r(28)-0.435,p(28)0.021),respectively.The expression level of plasma miRNA-320 a was positively correlated with LDH(r(28)0.531,p(28)0.004)and SCr(r(28)0.623,p(28)0.0004).The expression of plasma miRNA-320 a was not correlated with sex,age,hemophagy,Fbg and sCD25.5.ROC curve analysis showed that when the miR-125a-3p and miR-320 a were used in the diagnosis of HLH,their area under the curve(AUC)were 0.783 and 0.719,their sensitivity were 78.6% and 53.6%,their specificity were 66.7% and 93.3%,and their optimal critical values were 1.61 and 3.03,respectively.Conclusion:1.There is a specific miRNA expression profile in the plasma of HLH patients,which provides a new target for the pathogenesis and diagnosis of HLH.2.The expression of plasma miR-125a-3p and miR-320 a was significantly upregulated in HLH patients,suggesting that miR-125a-3p and miR-320 a may be closely related to the pathogenesis of HLH.3.The up-regulation of plasma miR-125a-3p was significantly correlated with the amount of WBC and ANC in HLH patients,suggesting that miR-125a-3p may be involved in the production of HLH cytokines and the activation of immune cells.The more significantly the miR-320 a expression was up-regulated,the more severe the liver and kidney function damage was in HLH patients,indicating that miR-320 a promoted inflammatory response.4.miR-125a-3p and miR-320 a may be potential biomarkers for the diagnosis of HLH.