Serum Angiopoietin-2 as Marker of Plasma Leakage in Dengue Viral Infection

Abstract

Background. The immunopathology of DHF/DSS is yet completely understood. Angiopoietin-2 (Ang-2) produced by endothelial cell could promote vascular leakage by disrupting endothelial junction. Few studies reported the role of Ang-2 in dengue viral infection. Objective. To study the role of Ang-2 in promoting vascular leakage in dengue viral infection. Methods. Prospective cohort study conducted at Prof. Dr. R.D. Kandou, Pancaran Kasih and R.W. Mongonsidi General Hospitals in Manado, from March 2013 to October 2014. Children, aged 1-15 years old, with the diagnosis of dengue viral infection according to 1997 World Health Organization (WHO) criteria [Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS)],were recruited consecutively. Written informed consent was obtained from parents or legal guardian. Blood samples were obtained at the time of diagnosis and 48 hours after, evaluated for complete blood counts, albumin, NS-1, Ig M, Ig G anti-dengue, and Ang-2. Results. During the study period, there were 119 children with dengue viral infections (39 DF, 39 DHF, 41 DSS). Patient’s characteristics: female predominance, age between 1.5-8.5 years old, well nourished, and mean albumin level were less than ≤3.5 gr% in the DHF and DSS group. Ang-2 level at admission were 2,486.21 pg/dl, 3,194.95 pg/dl and 4,005.32 pg/dl in DF, DHF and DSS group, respectively. Anova test analyses shows significant differences in serum Ang-2 level at admission between DF, DHF and DSS group (p<0.0001). Between those groups, DSS group had the highest level of Ang-2, followed with DHF and DF. Discussion. Mean albumin level were 3.88 gr%, 3.39 gr% and 2.63gr% in DF, DHF and DSS group, respectively. This results shows increasing plasma leakage with increasing severity of dengue viral infection. Increasing level of Ang-2 can promote blood vessels instability therefore causing increased vascular permeability and subsequent plasma leakage. In this study, we found significant elevation of serum Ang-2 in patiens with DSS compared to DHF and DF but the difference was not significant between DF and DHF group. Conclusions. Angiopoietin-2 contributes in transient systemic vascular leak in dengue viral infection.