Ikumi Matsushita1, Nguyen Thi Le Hang2, Le Thi Hong3, Do Bang Tam3, Luu Thi Lien4, Pham Huu Thuong5, Vu Cao Cuong4, Minako Hijikata6, Nobuyuki Kobayashi7, Shinsaku Sakurada8, Kazue Higuchi9, Nobuyuki Harada9, Naoto Keicho10. 1. Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis - Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan. 2. NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam. 3. Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam. 4. Hanoi Department of Health, Hanoi, Vietnam. 5. Hanoi Lung Hospital, Hanoi, Vietnam. 6. Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis - Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, Tokyo, Japan. 7. NHO Tokyo National Hospital, Tokyo, Japan. 8. Bureau of International Medical Cooperation, National Center for Global Health and Medicine, Tokyo, Japan. 9. Research Institute of Immune Diagnosis, Tokyo, Japan. 10. Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis - Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, Tokyo, Japan. Electronic address: nkeicho-tky@umin.ac.jp.
Abstract
OBJECTIVES: In the performance of interferon gamma release assays (IGRA) for the diagnosis of tuberculosis (TB) infection, false-negative results are a major obstacle. In active TB patients, treatment-dependent changes of the negative test results remain unknown. METHODS: The treatment course of 19 smear-positive/culture-confirmed TB patients who had IGRA-negative results by QuantiFERON-TB in-tube (QFT-IT) method at the time of diagnosis (month 0) in a previous study, were monitored in the present study. Blood was further collected at months 2 and 7, and the concentrations of 27 immune molecules were measured in the plasma supernatants remaining after performing the IGRA, using a suspension array system. RESULTS: After initiating treatment, eight of the 19 QFT-IT-negative patients showed positive conversion, whereas the remaining 11 (58%) did not; the interferon gamma (IFN-γ) response was restored to levels higher than 1 IU/ml in only three of the eight patients with positive conversion. Plasma concentrations of interleukin 1 receptor antagonist, interleukin 2, and interferon gamma-induced protein 10 remained low after Mycobacterium tuberculosis-specific antigen stimulation at months 2 and 7 in the continuously QFT-IT-negative group, whereas the parameters were elevated only in the transiently QFT-IT-negative group. CONCLUSIONS: It was demonstrated that a majority of active TB patients showing negative IGRA results did not regain sufficient levels of immune responsiveness despite successful treatment.
OBJECTIVES: In the performance of interferon gamma release assays (IGRA) for the diagnosis of tuberculosis (TB) infection, false-negative results are a major obstacle. In active TB patients, treatment-dependent changes of the negative test results remain unknown. METHODS: The treatment course of 19 smear-positive/culture-confirmed TB patients who had IGRA-negative results by QuantiFERON-TB in-tube (QFT-IT) method at the time of diagnosis (month 0) in a previous study, were monitored in the present study. Blood was further collected at months 2 and 7, and the concentrations of 27 immune molecules were measured in the plasma supernatants remaining after performing the IGRA, using a suspension array system. RESULTS: After initiating treatment, eight of the 19 QFT-IT-negative patients showed positive conversion, whereas the remaining 11 (58%) did not; the interferon gamma (IFN-γ) response was restored to levels higher than 1 IU/ml in only three of the eight patients with positive conversion. Plasma concentrations of interleukin 1 receptor antagonist, interleukin 2, and interferon gamma-induced protein 10 remained low after Mycobacterium tuberculosis-specific antigen stimulation at months 2 and 7 in the continuously QFT-IT-negative group, whereas the parameters were elevated only in the transiently QFT-IT-negative group. CONCLUSIONS: It was demonstrated that a majority of active TB patients showing negative IGRA results did not regain sufficient levels of immune responsiveness despite successful treatment.