Simon Geisler1, Simon D Lytton2, Nguyen Linh Toan3, Trinh Huu Nghia4, Nguyen Minh Nam4, Hoang Vu Hung4, Nguyen Thai Son4, Do Tuan Anh4, Hoang Tien Tuyen4, Tran Viet Tien4, Do Quyet4, Hoang Van Tong3, Nghiem Xuan Hoan5, Le Huu Song5, Srinivas Reddy Pallerla6, Johanna M Gostner7, Dietmar Fuchs1, Thirumalaisamy P Velavan8. 1. Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria. 2. SeraDiaLogistics, Munich, Germany. 3. Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Viet Nam. 4. 103 Military Hospital, Vietnam Military Medical University, Hanoi, Viet Nam. 5. 108 Military Central Hospital, Hanoi, Viet Nam; VG-CARE - Vietnamese-German Centre for Medical Research, VG-CARE, Hanoi, Viet Nam. 6. VG-CARE - Vietnamese-German Centre for Medical Research, VG-CARE, Hanoi, Viet Nam; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. 7. Division of Medical Biochemistry, Innsbruck Medical University, Innsbruck, Austria. 8. VG-CARE - Vietnamese-German Centre for Medical Research, VG-CARE, Hanoi, Viet Nam; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Faculty of Medicine, Duy Tan University, Da Nang, Viet Nam. Electronic address: velavan@medizin.uni-tuebingen.de.
Abstract
OBJECTIVES: During dengue fever, a pronounced gamma-interferon immune response produces neopterin and promotes tryptophan degradation by the enzyme indoleamine-2,3-dioxygenase 1 (IDO-1). Activated IDO-1 is indicated by an increased kynurenine to tryptophan ratio (Kyn/Trp) in patients. METHODS: Plasma levels of neopterin, kynurenine, and tryptophan were measured in 72 hospitalized dengue virus (DENV) patients and 100 healthy individuals. Plasma levels of neopterin, kynurenine, and tryptophan were also measured prospectively in a second cohort of 13 DENV patients; on the day of hospitalization, on day 2-3 at discharge, and 7-10 days after discharge. DENV RNA positivity was determined by qualitative and quantitative methodologies. RESULTS: DENV RNA-positive patients presented significantly higher levels of neopterin (mean 36.5nmol/l) and Kyn/Trp ratios (mean 102μmol/mmol) compared to DENV RNA-negative individuals. A significant correlation between neopterin levels and Kyn/Trp ratios was observed in both DENV RNA-positive (Spearman's rho=0.37, p< 0.01) and DENV RNA-negative (Spearman's rho=0.89, p<0.001) patients. Kyn/Trp ratios were negatively correlated with platelet counts (Spearman's rho=-0.43, p<0.01) and positively correlated with liver enzymes: AST (Spearman's rho=0.68, p<0.01) and ALT (Spearman's rho=0.51, p<0.05). In addition, the follow-up data presented a significant decrease in neopterin levels and Kyn/Trp ratios within 10 days after hospital entry. CONCLUSIONS: Neopterin levels and Kyn/Trp ratios were significantly increased in DENV patients and subsequently decreased after recovery.
OBJECTIVES: During dengue fever, a pronounced gamma-interferon immune response produces neopterin and promotes tryptophan degradation by the enzyme indoleamine-2,3-dioxygenase 1 (IDO-1). Activated IDO-1 is indicated by an increased kynurenine to tryptophan ratio (Kyn/Trp) in patients. METHODS: Plasma levels of neopterin, kynurenine, and tryptophan were measured in 72 hospitalized dengue virus (DENV) patients and 100 healthy individuals. Plasma levels of neopterin, kynurenine, and tryptophan were also measured prospectively in a second cohort of 13 DENV patients; on the day of hospitalization, on day 2-3 at discharge, and 7-10 days after discharge. DENV RNA positivity was determined by qualitative and quantitative methodologies. RESULTS: DENV RNA-positive patients presented significantly higher levels of neopterin (mean 36.5nmol/l) and Kyn/Trp ratios (mean 102μmol/mmol) compared to DENV RNA-negative individuals. A significant correlation between neopterin levels and Kyn/Trp ratios was observed in both DENV RNA-positive (Spearman's rho=0.37, p< 0.01) and DENV RNA-negative (Spearman's rho=0.89, p<0.001) patients. Kyn/Trp ratios were negatively correlated with platelet counts (Spearman's rho=-0.43, p<0.01) and positively correlated with liver enzymes: AST (Spearman's rho=0.68, p<0.01) and ALT (Spearman's rho=0.51, p<0.05). In addition, the follow-up data presented a significant decrease in neopterin levels and Kyn/Trp ratios within 10 days after hospital entry. CONCLUSIONS:Neopterin levels and Kyn/Trp ratios were significantly increased in DENV patients and subsequently decreased after recovery.
Authors: Thiara Manuele Alves de Souza; Caroline Fernandes-Santos; Jéssica Araújo da Paixão de Oliveira; Larissa Cristina Teixeira Tomé; Victor Edgar Fiestas-Solórzano; Priscila Conrado Guerra Nunes; Gabriel Macedo Costa Guimaraes; Juan Camilo Sánchez-Arcila; Iury Amâncio Paiva; Luís Jose de Souza; Paulo Vieira Damasco; Válber da Silva Frutuoso; Manoela Heringer; Luzia Maria de Oliveira-Pinto; Roberta Olmo Pinheiro; Flavia Barreto Dos Santos; Elzinandes Leal de Azeredo Journal: Pathogens Date: 2022-04-07
Authors: Rosa Bellmann-Weiler; Lukas Lanser; Francesco Burkert; Stefanie Seiwald; Gernot Fritsche; Sophie Wildner; Andrea Schroll; Sabine Koppelstätter; Katharina Kurz; Andrea Griesmacher; Günter Weiss Journal: Open Forum Infect Dis Date: 2020-11-03 Impact factor: 3.835
Authors: Alexander Lercher; Alexandra M Popa; Csilla Viczenczova; Lindsay Kosack; Kristaps Klavins; Benedikt Agerer; Christiane A Opitz; Tobias V Lanz; Michael Platten; Andreas Bergthaler Journal: PLoS Pathog Date: 2020-10-12 Impact factor: 6.823