Severity of plasma leakage is associated with high levels of IP-10 , HGF , MMP-2 and MMP-9 during dengue infections

Background. Dengue virus infection typically causes mild dengue fever, but in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occurs. The pathophysiological hallmark of DHF/DSS is plasma leakage that leads to enhanced vascular permeability likely due to cytokine storm. Methods. Ninety dengue patients from 2010-2012 in Singapore were prospectively recruited and stratified according to their diseases phase, primary and secondary infection status, and disease severity measured by plasma leakage. Clinical parameters were recorded throughout the disease progression. The levels of various immune mediators were quantified using comprehensive multiplex microbead-based immunoassays for 46 immune mediators. Results. Association between clinical parameters and immune mediators were analyzed using various statistical methods. Potential immune markers including IL1Ra, IP-10, HGF, sTNFRp75, VCAM-1 and MMP-2 were significantly associated with significant plasma leakage. Secondary DENV infections were also shown to influence disease outcome in terms of disease severity. Conclusions. This study identified several key markers for exacerbated dengue pathogenesis, notably plasma leakage. This will allow a better understanding of the molecular mechanisms of DHF/DSS in dengue patients. at C onell U niersity L irary on O cber 1, 2016 http://jidrdjournals.org/ D ow nladed from