Cytokine IP-10 and GM-CSF are prognostic biomarkers for severity in secondary dengue infection

Sankar, S.; Anand, Asha

doi:10.1016/j.humimm.2021.03.003

Cited by 12 publications

(13 citation statements)

References 70 publications

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“…The proportion of SD patients in our study is smaller than that detected in another study of DENV-infected patients in Yangon during the same period [ 15 ]. The most common presenting symptoms in the patients in our study were fever, vomiting, and headache, and both the frequency and type of symptoms were similar to those described in other studies of DENV infection in India [ 16 , 17 ].…”

Section: Discussionsupporting

confidence: 88%

Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019

Soe

Hamano

et al. 2022

Pathogens

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The dengue virus (DENV) has been endemic in Myanmar since 1970, causing outbreaks every 2–3 years. DENV infection symptoms range from mild fever to lethal hemorrhage. Clinical biomarkers must be identified to facilitate patient risk stratification in the early stages of infection. We analyzed 45 cytokines and other factors in serum samples from the acute phase of DENV infection (within 3–5 days of symptom onset) from 167 patients in Yangon, Myanmar, between 2017 and 2019. All of the patients tested positive for serum DENV nonstructural protein 1 antigen (NS1 Ag); 78.4% and 62.9% were positive for immunoglobulin M (IgM) and G (IgG), respectively; and 18.0%, 19.8%, and 11.9% tested positive for serotypes 1, 3, and 4, respectively. Although the DENV-4 viral load was significantly higher than those of DENV-1 or DENV-3, disease severity was not associated with viral load or serotype. Significant correlations were identified between disease severity and CCL5, SCF, PDGF-BB, IL-10, and TNF-α levels; between NS1 Ag and SCF, CCL5, IFN-α, IL-1α, and IL-22 levels; between thrombocytopenia and IL-2, TNF-α, VEGF-D, and IL-6 levels; and between primary or secondary infection and IL-2, IL-6, IL-31, IL-12p70, and MIP-1β levels. These circulating factors may represent leading signatures in acute DENV infections, reflecting the clinical outcomes in the dengue endemic region, Myanmar.

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Section: Discussionsupporting

confidence: 88%

Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019

Soe

Hamano

et al. 2022

Pathogens

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“… Priyadarshini and colleagues (2010) have shown increased level of IFNγ level in DF, which is similar to our study. Previously, we have shown gradual increase in IFNγ mRNA and protein within dengue severity of primary and secondary infection ( Gowri Sankar and Alwin Prem Anand, 2021 ). Significant upregulation was observed in primary infection compared to secondary infection of DENV-1, DENV-2, and DENV-4 ( Figure 6F ).…”

Section: Discussionmentioning

confidence: 89%

“…Recent reports show IP-10 has significant expression pattern in dengue-infected patients (Becquart et al, 2010;Malavige et al, 2012;Rathakrishnan et al, 2012;Zhao et al, 2016;Huang et al, 2018). Previously, we have shown significant increase in secondary DHF and DSS (Gowri Sankar and Alwin Prem Anand, 2021). In case of serotypes, IP-10 was higher in DENV-2 (Becquart et al, 2010), and no other reports were available for other serotypes.…”

Section: Ip-10 Expression In Denv Serotypesmentioning

confidence: 82%

“…Secondary heterotypic infection in severe dengue (DHF) shows increased levels of GM-CSF (Bozza et al, 2008;Friberg et al, 2018;Patro et al, 2019;Wang et al, 2019). Previously, we have reported significantly increased GM-CSF expression in DF, DHF, and DSS of secondary infection (Gowri Sankar and Alwin Prem Anand, 2021). In this study, we found significant upregulation in DENV-2 and 4 than control (Figure 5F), in secondary DENV-1, 2, and 4 than primary infection (Figure 6H, Figure S1), in DENV-2 DF and DSS than control (Figure S2B), and in DENV-4 DHF and DSS than control (Figure S2D).…”

Section: Gm-csf Expression In Denv Serotypesmentioning

confidence: 99%

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Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile

Sankar

Sundari²,

Anand

2021

Front. Cell. Infect. Microbiol.

Self Cite

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Dengue virus (DENV) infection is prevalent in tropical and subtropical regions of the world, which is fatal if untreated symptomatically. Emergence of new genotype within serotypes led to enhanced severity. The objective of the study is to identify the molecular characteristics of the DENV circulated during 2017 outbreak in Tamil Nadu, India, and to investigate the role of inflammatory cytokines in different “serotypes” and in “dengue severity”. A total of 135 suspected samples were tested for DENV infection using IgM, IgG, and qPCR assay; where 76 samples were positive for DENV and analyzed for 12 inflammatory cytokines using ELISA. Serotyping shows 14 DENV-1, 22 DENV-2, 7 DENV-3, and 33 DENV-4, where DENV-4 was predominant. Among 76, 42 isolates were successfully sequenced for C-prM region and grouped. A lineage shift was observed in DENV-4 genotype. Irrespective of serotypes, IFNγ was significantly elevated in all serotypes than control as well as in primary infection than secondary, indicating its role in immune response. GM-CSF and IP-10 were significantly elevated in secondary infection and could be used as prognostic biomarkers for secondary infection. Our observation shows differential cytokine expression profile varied with each serotype, indicating serotype/genotype-specific viral proteins might play a major role in dengue severity. DENV-4 as dominant serotype was reported in Tamil Nadu for the first time during an outbreak with a mixed Th1/Th17 cytokine expression profile that correlated with disease severity. We conclude it is essential to identify circulating viral genotype and their fitness by mutational analysis to correlate with disease severity and immune status, as this correlation will be helpful in diagnostics and therapeutics applications.

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“…Thus, high levels of CXCL10/IP-10 may limit the spread of infection [ 55 ]. In addition, another recent study showed that there was significant upregulation of CXCL10/IP-10 in secondary infection due to the dengue virus compared to the other cytokines analyzed [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus

Solórzano

Faria

Santos

et al. 2021

Viruses

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The incidence of dengue in Latin America has increased dramatically during the last decade. Understanding the pathogenic mechanisms in dengue is crucial for the identification of biomarkers for the triage of patients. We aimed to characterize the profile of cytokines (IFN-γ, TNF-α, IL-1β, IL-6, IL-18 and IL-10), chemokines (CXCL8/IL-8, CCL2/MCP-1 and CXCL10/IP-10) and coagulation mediators (Fibrinogen, D-dimer, Tissue factor-TF, Tissue factor pathway inhibitor-TFPI and Thrombomodulin) during the dengue-4 epidemic in Brazil. Laboratory-confirmed dengue cases had higher levels of TNF-α (p < 0.001), IL-6 (p = 0.005), IL-10 (p < 0.001), IL-18 (p = 0.001), CXCL8/IL-8 (p < 0.001), CCL2/MCP-1 (p < 0.001), CXCL10/IP-10 (p = 0.001), fibrinogen (p = 0.037), D-dimer (p = 0.01) and TFPI (p = 0.042) and lower levels of TF (p = 0.042) compared to healthy controls. A principal component analysis (PCA) distinguished between two profiles of mediators of inflammation and coagulation: protective (TNF-α, IL-1β and CXCL8/IL-8) and pathological (IL-6, TF and TFPI). Lastly, multivariate logistic regression analysis identified high aspartate aminotransferase-to-platelet ratio index (APRI) as independent risk factors associated with severity (adjusted OR: 1.33; 95% CI 1.03–1.71; p = 0.027), the area under the receiver operating characteristics curve (AUC) was 0.775 (95% CI 0.681–0.869) and an optimal cutoff value was 1.4 (sensitivity: 76%; specificity: 79%), so it could be a useful marker for the triage of patients attending primary care centers.

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Cytokine IP-10 and GM-CSF are prognostic biomarkers for severity in secondary dengue infection

Cited by 12 publications

References 70 publications

Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019

Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019

Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile

Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus

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