Janin Nouhin1, Polidy Pean2, Yoann Madec3, Mathieu F Chevalier4, Celine Didier4, Laurence Borand5, François-Xavier Blanc6, Daniel Scott-Algara4, Didier Laureillard7, Laurence Weiss8. 1. HIV/Hepatitis Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia; Université Paris Diderot-Paris 7, Sorbonne Paris-Cité, Paris, France. 2. Immunology Platform, Pasteur Institute in Cambodia, Phnom Penh, Cambodia. 3. Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France. 4. Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France. 5. Epidemiology and Public Health Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia. 6. Institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France. 7. Infectious and Tropical Diseases Department, University Hospital, Nîmes, France. 8. Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Paris, France; Université Paris Descartes, Sorbonne Paris-Cité, Paris, France. Electronic address: laurence.weiss@aphp.fr.
Abstract
OBJECTIVES: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment. METHODS: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time. RESULTS: At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)). CONCLUSIONS: None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients.
OBJECTIVES: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infectedpatients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment. METHODS: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time. RESULTS: At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)). CONCLUSIONS: None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infectedpatients.
Authors: Caian L Vinhaes; Deivide Oliveira-de-Souza; Paulo S Silveira-Mattos; Betania Nogueira; Ruiru Shi; Wang Wei; Xing Yuan; Guolong Zhang; Ying Cai; Clifton E Barry; Laura E Via; Kiyoshi F Fukutani; Bruno B Andrade; Katrin D Mayer-Barber Journal: Cytokine Date: 2019-06-18 Impact factor: 3.861
Authors: Eduardo P Amaral; Nicolas Riteau; Mahtab Moayeri; Nolan Maier; Katrin D Mayer-Barber; Rosana M Pereira; Silvia L Lage; Andre Kubler; William R Bishai; Maria R D'Império-Lima; Alan Sher; Bruno B Andrade Journal: Front Immunol Date: 2018-06-21 Impact factor: 7.561