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. 2016 Feb 17;13(3):179-86.
doi: 10.7150/ijms.13680. eCollection 2016.

Macrophage Activation Syndrome-Associated Markers in Severe Dengue

Hasliana Azrah Ab-Rahman  1 , Hafiz Rahim  2 , Sazaly AbuBakar  1 , Pooi-Fong Wong  3
Affiliations

Macrophage Activation Syndrome-Associated Markers in Severe Dengue

Hasliana Azrah Ab-Rahman et al. Int J Med Sci. .

Abstract

Hemophagocytosis, a phenomenon of which activated macrophages phagocytosed hematopoietic elements was reportedly observed in severe dengue patients. In the present study, we investigated whether markers of macrophage activation syndrome (MAS) can be used as differential diagnostic markers of severe dengue. Two hundred and eight confirmed dengue patients were recruited for the study. Sandwich ELISA was used to determine serum ferritin, soluble CD163 (sCD163), and soluble CD25 (sCD25) levels. The population of circulating CD163 (mCD163) monocytes was determined using flow cytometry. Receiver operating characteristic (ROC) analysis was plotted to determine the predictive validity of the biomarkers. Serum ferritin and sCD163 were found significantly increased in severe dengue patients compared to dengue fever patients (P = 0.003). A fair area under ROC curves (AUC) at 0.72 with a significant P value of 0.004 was observed for sCD163. sCD25 and mCD163 levels were not significantly different between severe dengue and dengue fever patients. Our findings suggest that in addition to serum ferritin, sCD163 can differentiate severe dengue from that of dengue fever patients. Hence, sCD163 level can be considered for use as a predictive marker for impending severe dengue.

Keywords: CD163; CD25.; Hemophagocytic lymphohistiocytosis; cytokine storm; macrophage hyperactivation.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Procedural workflow used for the confirmation of dengue.
Figure 2
Figure 2
Soluble Serum Biomarkers in Dengue. (A) Ferritin, (B) sCD163, (C) sCD25. One-way ANOVA test with Bonferroni's multiple comparison was performed using GraphPad Prism version 5.01 software. *P < 0.05, **P < 0.01, ***P < 0.001, ns indicates non-significant.
Figure 3
Figure 3
Correlation analysis and the receiver operating characteristic (ROC) curves of sCD163. (A) Correlation of serum ferritin to sCD163 in severe dengue patients, P=0.008. (B) ROC curve for sCD163 in severe dengue group in comparison to the dengue fever group. A fair area under ROC curves (AUC) at 0.72 was obtained. (C) ROC curve combining sCD163 and ferritin above than 10000 µg/L in the severe dengue group. A perfect AUC score at 1.00 was obtained.
Figure 4
Figure 4
Total population of circulating CD163-bearing monocytes in dengue patients. Gating strategy of CD163+ monocytes population originated from total monocytes of peripheral blood (4A). Lower population of CD163+ monocytes is observed in severe dengue (4B) compared to the healthy control group. *P < 0.05, **P < 0.01, ***P < 0.001.
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References

    1. AbuBakar S, Shafee N. Outlook of dengue in Malaysia: a century later. Malays J Pathol. 2002;24:23–27. - PubMed
    1. Brady OJ, Gething PW, Bhatt S. et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6:e1760. - PMC - PubMed
    1. Duong V, Lambrechts L, Paul RE. et al. Asymptomatic humans transmit dengue virus to mosquitoes. Proc Natl Acad Sci U S A. 2015;112:14688–93. - PMC - PubMed
    1. Ho TS, Wang SM, Anderson R, at al. Antibodies in dengue immunopathogenesis. J Formos Med Assoc. 2013;112:1–2. - PubMed
    1. de Alwis R, Williams KL, Schmid MA, Lai CY, Patel B, Smith SA. Dengue viruses are enhanced by distinct populations of serotype cross-reactive antibodies in human immune sera. PLoS Pathog. 2014;10:e1004386. - PMC - PubMed

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