title: Dynamics of immune parameters during the treatment of active tuberculosis showing negative interferon gamma response at the time of diagnosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis - Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.affiliation: NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.
authors.forename: Nguyen Thi Le
authors.initials: NT
authors.lastname: Hang
authors.affiliation: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Le Thi
authors.initials: le T
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Do Bang
authors.initials: do B
authors.lastname: Tam
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: Luu Thi
authors.initials: LT
authors.lastname: Lien
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Pham Huu
authors.initials: PH
authors.lastname: Thuong
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: Vu Cao
authors.initials: VC
authors.lastname: Cuong
authors.affiliation: 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.
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.affiliation: NHO Tokyo National Hospital, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Bureau of International Medical Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Sakurada
authors.affiliation: Research Institute of Immune Diagnosis, Tokyo, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Research Institute of Immune Diagnosis, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada
authors.affiliation: 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.
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D059425:Interferon-gamma Release Tests; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D007371:Interferon-gamma
keywords: False-negative result; Interferon gamma release assay; Interferon gamma-induced protein 10; Interleukin 1 receptor antagonist; Interleukin 2; Sensitivity