Correlation Between Serum Levels of Anti-Endothelial Cell Autoantigen and Anti-Dengue Virus Nonstructural Protein 1 Antibodies in Dengue Patients

Cheng, Hsien Jen; Luo, Yueh Hsia; Wan, Shu; Lin, Chiou Feng; Wang, Shan Tair; Hưng, Nguyễn Thành; Liu, Ching Chuan; Ho, Tzong Shiann; Liu, Hsiao Sheng; Yeh, Trai Ming; Lin, Yee Shin

doi:10.4269/ajtmh.14-0162

Cited by 16 publications

(18 citation statements)

References 70 publications

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“…Thus, it is possible that other mAbs binding this C-terminal epitope could provide cross-protection against other flaviviruses, although this warrants further examination. Whereas we observed a protective effect against ZIKV following passive administration of group C mAbs, some anti-DENV NS1 antibodies that bind C-terminal epitopes (particularly residues 305–330) reportedly react with human endothelial cells, platelets, and plasminogen, and are speculated to contribute to pathogenesis 52 – 54 .…”

Section: Discussionmentioning

confidence: 60%

Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

et al. 2020

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There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.

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Section: Discussionmentioning

confidence: 60%

Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

et al. 2020

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“…Instead, these virus-immune complexes are recognized by Fcγ receptor-bearing cells that facilitate virus entry and replication, resulting in increased disease severity [14,15]. Host protein cross-reactivity with DENV proteins has also been suggested to contribute to the pathogenesis of dengue [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Multivariate time-series analysis of biomarkers from a dengue cohort offers new approaches for diagnosis and prognosis

et al. 2020

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Dengue is a major public health problem worldwide with distinct clinical manifestations: an acute presentation (dengue fever, DF) similar to other febrile illnesses (OFI) and a more severe, life-threatening form (severe dengue, SD). Due to nonspecific clinical presentation during the early phase of dengue infection, differentiating DF from OFI has remained a challenge, and current methods to determine severity of dengue remain poor early predictors. We present a prospective clinical cohort study conducted in Caracas, Venezuela from 2001-2005, designed to determine whether clinical and hematological parameters could distinguish DF from OFI, and identify early prognostic biomarkers of SD. From 204 enrolled suspected dengue patients, there were 111 confirmed dengue cases. Piecewise mixed effects regression and nonparametric statistics were used to analyze longitudinal records. Decreased serum albumin and fibrinogen along with increased D-dimer, thrombin-antithrombin complex, activated partial thromboplastin time and thrombin time were prognostic of SD on the day of defervescence. In the febrile phase, the day-today rates of change in serum albumin and fibrinogen concentration, along with platelet counts, were significantly decreased in dengue patients compared to OFI, while the day-today rates of change of lymphocytes (%) and thrombin time were increased. In dengue patients, the absolute lymphocytes to neutrophils ratio showed specific temporal increase, enabling classification of dengue patients entering the critical phase with an area under the ROC curve of 0.79. Secondary dengue patients had elongation of Thrombin time compared to primary cases while the D-dimer formation (fibrinolysis marker) remained always lower for secondary compared PLOS NEGLECTED TROPICAL DISEASES

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“…Upon presentation early after disease onset, it is clinically impossible to differentiate dengue virus (DENV)-infected patients who will have an unremarkable DF disease episode from those who will progress to potentially fatal DHF/DSS [ 3 – 7 ]. Viral biomarkers that correlate with dengue severity include viremia titer and nonstructural protein 1 (NS1) concentration in the blood, secondary DENV infection, and infection with specific virus genotypes [ 8 – 11 ]. Host biomarkers associated with disease severity include multiple immune molecules, biochemical and physiological response indicators, and genetic polymorphisms [ 3 , 4 , 12 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

et al. 2016

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BackgroundEpidemic dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and clinical care of dengue patients throughout the tropical and subtropical world. The ability to predict severe dengue disease outcomes (DHF/DSS) using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management. Advances in the field of metabolomics and analytic software provide new opportunities to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that differentiate dengue disease outcomes.Methodology/Principal FindingsExploratory metabolomic studies were conducted to characterize the serum metabolome of patients who experienced different dengue disease outcomes. Serum samples from dengue patients from Nicaragua and Mexico were retrospectively obtained, and hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) identified small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. In the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes. In the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS). Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. Differential perturbation of the serum metabolome was demonstrated following infection with different DENV serotypes and following primary and secondary DENV infections.Conclusions/SignificanceThese results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum specimens that are associated with distinct DENV infections and disease outcomes. The differentiating metabolites also provide insights into metabolic pathways and pathogenic and immunologic mechanisms associated with dengue disease severity.

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Correlation Between Serum Levels of Anti-Endothelial Cell Autoantigen and Anti-Dengue Virus Nonstructural Protein 1 Antibodies in Dengue Patients

Cited by 16 publications

References 70 publications

Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

Multivariate time-series analysis of biomarkers from a dengue cohort offers new approaches for diagnosis and prognosis

Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

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