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Observational Study
. 2017 Mar 15;215(6):992-999.
doi: 10.1093/infdis/jix041.

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection

Suhendro Suwarto  1 , R Tedjo Sasmono  2 , Robert Sinto  1 , Eppy Ibrahim  3 , Maulana Suryamin  3
Affiliations
Observational Study

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection

Suhendro Suwarto et al. J Infect Dis. .

Abstract

Background: The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage.

Methods: A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage.

Results: A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025-1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004-1.074) had an adjusted association with severe plasma leakage.

Conclusions: In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

Keywords: chondroitin sulfate; claudin-5; dengue infection; plasma leakage; syndecan-1.

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Figures

Figure 1.
Figure 1.
Scatter plot of the serum interleuking 10 (IL-10) levels in the dengue fever (DF), dengue hemorrhagic fever (DHF), and severe plasma leakage groups. The horizontal bars represent the median serum IL-10 levels. Differences in the median between pairs of groups were tested using the Mann–Whitney test (P = .03 for the difference between the DF and the DHF groups; P = .02 for the difference between the DF and the severe plasma leakage groups).
Figure 2.
Figure 2.
Scatter plot of the serum chemokine (C-X-C motif) ligand 10/interferon γ-inducible protein 10 (CXCL10/IP10) levels in the dengue fever (DF), dengue hemorrhagic fever (DHF), and severe plasma leakage groups. The horizontal bars represent the median serum CXCL10/IP10 levels. Differences in the median between pairs of groups were tested using the Mann–Whitney test (P = .01 for the difference between the DF and the DHF groups; P = .006 for the difference between the DF and the severe plasma leakage groups).
Figure 3.
Figure 3.
Proposed mechanism of microvascular leakage in dengue infection. Plasma leakage: dengue virus (DENV) nonstructural protein 1 (NS1)–induced degradation of syndecan-1 and chondroitin sulfate results in gp60 activation by albumin. Gp60 activation leads to phosphorylation of the Src protein tyrosine kinases (PTKs) and caveolin-1, which is responsible for regulation of caveolar fission. Cytokines and chemokines can also stimulate activation of Src PTKs. This process increases albumin exocytosis through the transcellular pathway. Severe plasma leakage: Claudin-5 degradation causes retraction of endothelial cells and opening of intercellular gaps, allowing albumin movement into the extravascular space through paracellular pathways. Albumin leakage that occurs through both paracellular and transcellular pathways results in severe plasma leakage.
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References

    1. Rajapakse S, Rodrigo C, Maduranga S, Rajapakse AC. Corticosteroids in the treatment of dengue shock syndrome. Infect Drug Resist 2014; 7:137–43. - PMC - PubMed
    1. Srikiatkhachorn A, Krautrachue A, Ratanaprakarn W, et al. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr Infect Dis J 2007; 26:283–90; discussion 91–2. - PubMed
    1. Suwarto S, Nainggolan L, Sinto R, et al. Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection. BMC Infect Dis 2016; 16:322. - PMC - PubMed
    1. Srikiatkhachorn A. Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 2009; 102:1042–9. - PMC - PubMed
    1. de Azeredo EL, Monteiro RQ, de-Oliveira Pinto LM. Thrombocytopenia in dengue: interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediators Inflamm 2015; 2015:313842. - PMC - PubMed

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