Monika M Vivekanandan1, Ernest Adankwah1, Wilfred Aniagyei1, Isaac Acheampong1, Augustine Yeboah1, Joseph F Arthur1, Millicent N K Lamptey1, Mohammed K Abass2, Amidu Gawusu3, Francis Kumbel4, Francis Osei-Yeboah5, Linda Batsa Debrah1, Dorcas O Owusu1, Alexander Debrah1, Ertan Mayatepek6, Julia Seyfarth6, Richard O Phillips1,7, Marc Jacobsen8. 1. Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana. 2. Agogo Presbyterian Hospital, Agogo, Ghana. 3. Sene West Health Directorate, Kwame Danso, Ghana. 4. St. Mathias Catholic Hospital, Yeji, Ghana. 5. Atebubu District Hospital, Atebubu, Ghana. 6. Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine University, 40225, Duesseldorf, Germany. 7. School of Medicine and Dentistry, College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. 8. Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Duesseldorf, Heinrich-Heine University, 40225, Duesseldorf, Germany. marc.jacobsen@med.uni-duesseldorf.de.
Abstract
BACKGROUND: Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery. STUDY DESIGN AND METHODS: In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses. RESULTS: Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders. CONCLUSIONS: Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response.
BACKGROUND: Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery. STUDY DESIGN AND METHODS: In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses. RESULTS: Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders. CONCLUSIONS: Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response.
Authors: Fabiana A Zambuzi; Priscilla M Cardoso-Silva; Milena S Espindola; Luana S Soares; Leonardo J Galvão-Lima; Verônica S Brauer; Matheus S Gomes; Laurence R Amaral; Matthew Schaller; Valdes R Bollela; Fabiani G Frantz Journal: Cytokine Date: 2016-08-31 Impact factor: 3.861
Authors: Ernest Adankwah; Jean De Dieu Harelimana; Difery Minadzi; Wilfred Aniagyei; Mohammed K Abass; Linda Batsa Debrah; Dorcas O Owusu; Ertan Mayatepek; Richard O Phillips; Marc Jacobsen Journal: J Immunol Date: 2021-04-28 Impact factor: 5.422
Authors: Ernest Adankwah; Christian Lundtoft; Alptekin Güler; Kees L M C Franken; Tom H M Ottenhoff; Ertan Mayatepek; Ellis Owusu-Dabo; Richard Odame Phillips; Norman Nausch; Marc Jacobsen Journal: Front Immunol Date: 2019-07-03 Impact factor: 7.561