Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue

Dengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore...

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Main Authors: Win Khaing, Suk Hiang Lau, Tun-Linn Thein, Nguan Soon Tan, Sylvie Alonso, Shawn Vasoo, Po Ying Chia, David Chien Boon Lye, Yee Sin Leo, Vincent T. K. Chow
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/2/226
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author Win Khaing
Suk Hiang Lau
Tun-Linn Thein
Nguan Soon Tan
Sylvie Alonso
Shawn Vasoo
Po Ying Chia
David Chien Boon Lye
Yee Sin Leo
Vincent T. K. Chow
author_facet Win Khaing
Suk Hiang Lau
Tun-Linn Thein
Nguan Soon Tan
Sylvie Alonso
Shawn Vasoo
Po Ying Chia
David Chien Boon Lye
Yee Sin Leo
Vincent T. K. Chow
author_sort Win Khaing
collection DOAJ
description Dengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore adults. Plasma samples from 48 dengue patients (24 severe and 24 non-severe) during acute and convalescent phases were selected from the prospective COhort study on progression of DENgue severity in Singapore adults (CODEN) cohort. The CODEN was conducted at the National Centre for Infectious Diseases, Tan Tock Seng Hospital, from June 2016 to January 2020. ANGPTL4 levels were measured and compared to 152 healthy controls. Logistic regression assessed the relationship between plasma ANGPTL4 concentrations and disease severity. There were no statistically significant differences in ANGPTL4 levels between severe and non-severe dengue patients during acute (677.4 vs. 909.1 pg/mL, <i>p</i> = 0.4) or convalescent phases (793.7 vs. 565.6 pg/mL, <i>p</i> = 0.96). Plasma ANGPTL4 levels were significantly elevated during acute dengue (4634.3 pg/mL) versus healthy controls (907.4 pg/mL), declining during convalescence. Compared to the lowest tertile, the adjusted odds ratios for severe dengue were 0.36 (95%CI: 0.08–1.65, <i>p</i> = 0.190) for medium tertile and 0.57 (95%CI: 0.13–2.49, <i>p</i> = 0.456) for high tertile. Among patients with high ANGPTL4 levels (>5000 pg/mL), 36.4% developed severe complications, including significant plasma leakage. Plasma ANGPTL4 levels were significantly higher in dengue patients than controls, suggesting its potential as a biomarker, which warrants future detailed investigations. Larger prospective studies with serial sampling, including pediatric populations, may clarify the role of ANGPTL4 in severe dengue.
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spelling doaj-art-b824201fba8b4fd3afd311d509bf48c12025-08-20T02:45:42ZengMDPI AGViruses1999-49152025-02-0117222610.3390/v17020226Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with DengueWin Khaing0Suk Hiang Lau1Tun-Linn Thein2Nguan Soon Tan3Sylvie Alonso4Shawn Vasoo5Po Ying Chia6David Chien Boon Lye7Yee Sin Leo8Vincent T. K. Chow9National Centre for Infectious Diseases, Singapore 308442, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeNational Centre for Infectious Diseases, Singapore 308442, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeNational Centre for Infectious Diseases, Singapore 308442, SingaporeNational Centre for Infectious Diseases, Singapore 308442, SingaporeNational Centre for Infectious Diseases, Singapore 308442, SingaporeNational Centre for Infectious Diseases, Singapore 308442, SingaporeInfectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, SingaporeDengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore adults. Plasma samples from 48 dengue patients (24 severe and 24 non-severe) during acute and convalescent phases were selected from the prospective COhort study on progression of DENgue severity in Singapore adults (CODEN) cohort. The CODEN was conducted at the National Centre for Infectious Diseases, Tan Tock Seng Hospital, from June 2016 to January 2020. ANGPTL4 levels were measured and compared to 152 healthy controls. Logistic regression assessed the relationship between plasma ANGPTL4 concentrations and disease severity. There were no statistically significant differences in ANGPTL4 levels between severe and non-severe dengue patients during acute (677.4 vs. 909.1 pg/mL, <i>p</i> = 0.4) or convalescent phases (793.7 vs. 565.6 pg/mL, <i>p</i> = 0.96). Plasma ANGPTL4 levels were significantly elevated during acute dengue (4634.3 pg/mL) versus healthy controls (907.4 pg/mL), declining during convalescence. Compared to the lowest tertile, the adjusted odds ratios for severe dengue were 0.36 (95%CI: 0.08–1.65, <i>p</i> = 0.190) for medium tertile and 0.57 (95%CI: 0.13–2.49, <i>p</i> = 0.456) for high tertile. Among patients with high ANGPTL4 levels (>5000 pg/mL), 36.4% developed severe complications, including significant plasma leakage. Plasma ANGPTL4 levels were significantly higher in dengue patients than controls, suggesting its potential as a biomarker, which warrants future detailed investigations. Larger prospective studies with serial sampling, including pediatric populations, may clarify the role of ANGPTL4 in severe dengue.https://www.mdpi.com/1999-4915/17/2/226dengueangiopoietin-like 4endothelial dysfunctionplasma leakagedisease severityhealthy controls
spellingShingle Win Khaing
Suk Hiang Lau
Tun-Linn Thein
Nguan Soon Tan
Sylvie Alonso
Shawn Vasoo
Po Ying Chia
David Chien Boon Lye
Yee Sin Leo
Vincent T. K. Chow
Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
Viruses
dengue
angiopoietin-like 4
endothelial dysfunction
plasma leakage
disease severity
healthy controls
title Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
title_full Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
title_fullStr Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
title_full_unstemmed Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
title_short Elevated Plasma Angiopoietin-like 4 Protein Levels in Adult Patients with Dengue
title_sort elevated plasma angiopoietin like 4 protein levels in adult patients with dengue
topic dengue
angiopoietin-like 4
endothelial dysfunction
plasma leakage
disease severity
healthy controls
url https://www.mdpi.com/1999-4915/17/2/226
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