The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes.

Jing Guo,Huandi Zhou,Jingdong Zhu,Chunmei Wang,Nanshan Zhong,Shigui Yang,Mei Zeng,Haixia Xiao,Fengming Huang,Xuetao Cao,Ying Wu,Li Shao,Lanjuan Li,Yida Yang,Jiezuan Yang,Yu Chen,Kunkai Su,Bin Cao,Min Zhao,Yan Zhao,Song Liu,George F Gao,Jianwei Wang,Qiang Liu,Hainv Gao,Changjun Bao,Xiaoli Liu,Wei Wang,Li Wang,Chengyu Jiang,Dangsheng Li,Shuguang Tan,Weifeng Liang,Jianmin Zhang,Hongyan Diao,Xiaoqing Xu,Zhen Zou,Hui Li,Shufa Zheng,Cao H ,Jun Li ,Jianping Xu ,Jinren Pan

doi:10.1038/srep10942

Abstract

The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.

Highlights

In 2013, 144 people in eastern China had been confirmed infected with influenza A H7N9, a novel avian-origin influenza A reassortant subtype virus, with 48 people reported death[1,2,3,4,5]
We showed that a plasma profile of hypercytokinemia dynamics signature proteins including MIF, SCF, HGF, MCP-1, SCGF-β, IP-10, IL-18, and IFN-γ is dynamic biomarker to predict fatal outcomes
The P values of the other reported significantly elevated cytokines and chemokines in plasma samples of H7N9-infected patients in this study including β -nerve growth factor (β -NGF), IL-6, MIG, IL-8, MIP-1β, SDF-1α, CTACK, MIP-1α, IL-1ra, IL-9, IL-10, G-CSF, IL-7, IL-5, GM-CSF, IL-1β, IL-4, VEGF, TNF-α, IL-13, IL-2, basic-FGF, IL-12p70, PDGF-bb, IL-17A, and RANTES are not significant to predict fatal outcomes (Supplemental table S3). These results suggest that the levels of the hypercytokinemia factors MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ can be biomarkers that predict fatal outcomes for H7N9-infected patients

Summary

Result

The P values of the other reported significantly elevated cytokines and chemokines in plasma samples of H7N9-infected patients in this study including β -NGF, IL-6, MIG, IL-8, MIP-1β , SDF-1α , CTACK, MIP-1α , IL-1ra, IL-9, IL-10, G-CSF, IL-7, IL-5, GM-CSF, IL-1β , IL-4, VEGF, TNF-α , IL-13, IL-2, basic-FGF, IL-12p70, PDGF-bb, IL-17A, and RANTES are not significant to predict fatal outcomes (Supplemental table S3). These results suggest that the levels of the hypercytokinemia factors MIF, SCF, MCP-1, HGF, SCGF-β , IP-10, IL-18, and IFN-γ can be biomarkers that predict fatal outcomes for H7N9-infected patients. The profile of these 8 cytokines and chemokines was a statistically independent outcome predictor (Table 3)

Discussion

Methods