甲型H1N1流行性感冒患者疾病严重程度预测指标的初探

Preliminary study on predictive indicators of disease severity in patients with influenza A(H1N1)

目的分析轻症和重症甲型H1N1流行性感冒(以下简称流感)患者外周血转录组的差异,评估影响患者疾病严重程度的指标。方法纳入2018年1月至5月上海复旦大学附属华山医院确诊的10例甲型H1N1流感患者(轻症组与重症组各5例),以健康人群(5名)作为对照。采集研究对象的外周血进行RNA转录组测序并分析其结果。计量资料比较采用t检验和Mann-Whitney U检验,计数资料比较采用Fisher确切概率法。转录组测序结果的数据分析采用生物信息学方法。结果重症组患者血小板计数为(163.4±21.5)×109/L,低于轻症组患者的(255.6±52.5)×109/L,差异有统计学意义(t=3.636,P=0.007)。两组患者的性别、年龄、白细胞计数、中性粒细胞比例、淋巴细胞比例和血红蛋白值的差异均无统计学意义(均P>0.05)。外周血转录组研究结果显示,重症组患者的外周血基质金属蛋白酶8(matrix metalloproteinase 8,MMP8)测序结果的平均值为18.41,高于轻症组的2.33及健康对照组的1.43,差异均有统计学意义(均P<0.01)。基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)的平均值在重症组为174.00,高于轻症组的22.91和健康对照组的34.65,差异均有统计学意义(均P<0.01)。结论MMP8及MMP9有望作为判断甲型H1N1流感患者疾病严重程度的分子生物学标志物。

Objective To analyze the differences of peripheral blood transcriptome between mild and severe influenza A(H1N1)patients,and to find indicators for the assessment of disease severity.Methods A total of ten patients(five patients with mild disease and five patients with severe disease)diagnosed with H1N1 infection from January to May 2018 at Huashan Hospital,Fudan University in Shanghai were enrolled,and five healthy people were also enrolled as controls.The peripheral blood of patients was collected for transcriptome sequencing at the time when they were first diagnosed.Measurement data were compared using t test or Mann-Whitney U test.The count data were compared using Fisher exact test when appropriate.Data analysis of transcriptome predictions was performed using bioinformatics methods.Results The platelet counts were significantly different between mild and severe groups((163.4±21.5)×109/L vs(255.6±52.5)×109/L,t=3.636,P=0.007).There were no differences between the two groups in gender,age,white blood cell counts,neutrophil percentage,lymphocyte percentage and hemoglobin levels(all P>0.05).However,the average expression levels of matrix metalloproteinase(MMP)8 and MMP9 in severe group(18.41 and 174.00,respectively)were both higher than those in mild group(2.33 and 22.91,respectively)and healthy control(1.43 and 34.65,respectively;all P<0.01).Conclusion MMP8 and MMP9 could be expected to serve as the molecular biological markers for predicting the disease severity in patients with influenza A(H1N1)infection.