Thomas Blauenfeldt1, Dirk Wagner2, Martine Aabye3, Jan Heyckendorf4, Berit Lange2, Christoph Lange5, Martin Ernst4, Pernille Ravn6, Raquel Duarte7, Clara Morais8, Matthias Hoffmann9, Otto D Schoch10, Jose Dominguez11, Irene Latorre11, Morten Ruhwald12. 1. Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. 2. Department of Infectious Diseases and Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Freiburg, Germany. 3. Department of Double Diagnosis, Mental Health Centre Sct. Hans, Roskilde, Denmark. 4. Division of Clinical Infectious Diseases, Research Center Borstel, Germany. 5. Division of Clinical Infectious Diseases, Research Center Borstel, Germany; German Center for Infection Research Tuberculosis Unit International Health/Infectious Diseases, University of Lübeck, Germany; Department of Internal Medicine, University of Namibia School of Medicine, Windhoek, Namibia; Department of Medicine, Karolinska Institute, Stockholm, Sweden. 6. Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark. 7. Tuberculosis Outpatient Centre Vila Nova de Gaia, Portugal; Hospital Centre of Vila Nova de Gaia/Espinho, Portugal; Medical School, Porto University, Portugal; Institute of Public Health, Porto University, Portugal. 8. Pulmonology Diagnostic Center Porto and Vila Nova de Gaia, Portugal. 9. Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St.Gallen, Switzerland. 10. Division of Pneumology, Department of Internal Medicine, Cantonal Hospital St.Gallen, Switzerland. 11. Servei de Microbiologia, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ciber Enfermedades Respiratorias, Instituto de Salud Carlos III, Badalona, Spain. 12. Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. Electronic address: moru@ssi.dk.
Abstract
INTRODUCTION: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher temperatures could affect IFN-γ and IP-10 responsiveness in order to improve the performance of IP-10 release assays and IGRAs. AIM: The aim of this study was to assess the robustness of whole blood based IP-10 release assay and IGRAs and the effect of hyper-thermic incubation (39 °C) on the diagnostic accuracy of IP-10 release assay and IGRAs. RESULTS: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0.57-1.02) fold, with 39 °C compared to 37 °C incubation temperature. At 37 °C IGRA sensitivity was 85% and IP-10 sensitivity was 82%, whereas specificity was 97% for both tests (p > 0.8). These minor changes observed as a result of hyper-thermic incubation were not sufficient to impact IGRA and IP-10 release assay test performance. CONCLUSION: The performance of IGRA and IP-10 release assays is robust despite variations in the incubation temperature between 37 °C and 39 °C.
INTRODUCTION: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher temperatures could affect IFN-γ and IP-10 responsiveness in order to improve the performance of IP-10 release assays and IGRAs. AIM: The aim of this study was to assess the robustness of whole blood based IP-10 release assay and IGRAs and the effect of hyper-thermic incubation (39 °C) on the diagnostic accuracy of IP-10 release assay and IGRAs. RESULTS: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0.57-1.02) fold, with 39 °C compared to 37 °C incubation temperature. At 37 °C IGRA sensitivity was 85% and IP-10 sensitivity was 82%, whereas specificity was 97% for both tests (p > 0.8). These minor changes observed as a result of hyper-thermic incubation were not sufficient to impact IGRA and IP-10 release assay test performance. CONCLUSION: The performance of IGRA and IP-10 release assays is robust despite variations in the incubation temperature between 37 °C and 39 °C.
Authors: Xia Qiu; Tao Xiong; Xiaojuan Su; Yi Qu; Long Ge; Yan Yue; Yan Zeng; Wenxing Li; Peng Hu; Dezhi Mu Journal: BMC Infect Dis Date: 2019-10-30 Impact factor: 3.090