Association between dengue severity and plasma levels of dengue-specific IgE and chymase

Inokuchi, Miho; Dumre, Shyam Prakash; Mizukami, Shusaku; Tun, Mya Myat Ngwe; Kamel, Mohamed Gomaa; Manh, Dao Huy; Phuc, Le Hong; Thường, Nguyễn Văn; An, Tran Van; Weiss, Lan; Turk, Tarek; Đăng, Trần Ngọc; Huong, Vû Thi Quê; Morita, Kouichi; Huy, Nguyen Tien; Hirayama, Kenji

doi:10.1007/s00705-018-3849-z

Cited by 15 publications

(16 citation statements)

References 28 publications

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“…Increased vascular permeability, the hallmark of severe dengue, is thought to be provoked by mast cells ( 48 ). We and others have previously shown the important role of mast cell-derived mediators, including vascular endothelial growth factor (VEGF), tryptase, chymase, in vascular permeability in dengue severity ( 19 , 48 , 49 ). However, it is still unknown why the onset of vascular leakage occurs during defervescence.…”

Section: Discussionmentioning

confidence: 99%

“…This was a hospital-based prospective study conducted at Nguyen Dinh Chieu Hospital, Ben Tre province, Vietnam, from July 2011 to May 2013. The inclusion and exclusion criteria have been described elsewhere in our previous report (19) and provided in the Supplementary Materials. In our design, after the identification of dengue patients who met the inclusion criteria, they were required to be hospitalized despite having no severe manifestations at the time of recruitment.…”

Section: Study Design and Patient Recruitmentmentioning

confidence: 99%

“…Dengue was screened by DENV NS1 antigen ELISA kit (Bio-Rad Laboratories, Inc., Marnes-la-Coquette, France) and confirmed by either DENV RNA RT-PCR or MAC-ELISA as described elsewhere (19,20). In-house IgM/IgG capture ELISA assays (PIHCM, Vietnam) in paired sera (acute and convalescent) were performed to identify primary and secondary dengue infections where the secondary was defined as IgM/IgG ratio <1.8 and ≥4-fold rise of the IgG, respectively (20,21).…”

Section: Dengue Diagnosismentioning

confidence: 99%

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Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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Background: The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development. Objectives: This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. Study design: In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. Results: We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8 + T cells compared to mild cases at day −1 (p = 0.017) and day 0 (p = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4 + T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic.

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Section: Discussionmentioning

confidence: 99%

Section: Study Design and Patient Recruitmentmentioning

confidence: 99%

Section: Dengue Diagnosismentioning

confidence: 99%

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Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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“…Mast cells are shown to be permissive to infection by the DENV, which is enhanced in the presence of DENV-specific antibodies Syenina et al, 2015). Many proteases and inflammatory mediators produced by mast cells such as chymases, tryptases, platelet activating factor (PAF) and vascular endothelial growth factor (VEGF) have been implicated in vascular leak and disease pathogenesis (Furuta et al, 2012;Jeewandara et al, 2015;Kamaladasa et al, 2016;Tissera et al, 2017;Inokuchi et al, 2018;Malavige et al, 2018). As mast cells reside in tissues and around blood vessels, it has been difficult to determine their infectivity rates by the DENV and phenotypic changes .…”

Section: Mast Cells In Denguementioning

confidence: 99%

Dysfunctional Innate Immune Responses and Severe Dengue

Malavige

Jeewandara

Ogg

2020

Front. Cell. Infect. Microbiol.

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Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue.

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“…Unfortunately, there is no reliable routine prognostic test available yet [ 9 ]. There have been growing efforts made on the discovery of predictors based on severity biomarkers alone or in combination with dengue clinical signs [ 8 – 11 ], however these are either not validated clinically or the evidence is not adequate for clinical application [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue

Phuong

Manh

Dumre

et al. 2019

Ann Clin Microbiol Antimicrob

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BackgroundConsiderable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase.MethodsThis was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6–48 h before defervescence) were used to estimate the level of cfDNA.ResultsOf the 61 dengue patients, SD patients (n = 8) developed shock syndrome in 4.8 days (95% CI 3.7–5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55–0.88; p = 0.0493).ConclusionsTaken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.Electronic supplementary materialThe online version of this article (10.1186/s12941-019-0309-x) contains supplementary material, which is available to authorized users.

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Association between dengue severity and plasma levels of dengue-specific IgE and chymase

Cited by 15 publications

References 28 publications

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Dysfunctional Innate Immune Responses and Severe Dengue

Plasma cell-free DNA: a potential biomarker for early prediction of severe dengue

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