title: Association between tuberculosis recurrence and interferon-γ response during treatment.
abstract: OBJECTIVE
  We investigated the relationship between tuberculosis recurrence and Mycobacterium tuberculosis antigen-stimulated interferon-gamma (IFN-γ) responses during treatment.
  
  
  METHODS
  Plasma IFN-γ levels in active pulmonary tuberculosis patients (n = 407) were analyzed using QuantiFERON-TB Gold In-Tube™ (QFT-IT) at 0, 2, and 7 months of the 8-month treatment received from 2007 to 2009 and the patients were followed up for another 16 months after treatment. Risk factors for recurrence were assessed using the log-rank test and Cox proportional hazard models. Random coefficient models were used to compare longitudinal patterns of IFN-γ levels between groups.
  
  
  RESULTS
  QFT-IT showed positive results in 95.6%, 86.2%, and 83.5% at 0, 2, and 7 months, respectively. The antigen-stimulated IFN-γ responses varied significantly during the treatment course (P < 0.0001). Unexpectedly, positive-to-negative conversion of QFT-IT results between 0 and 2 months was significantly associated with earlier recurrence (adjusted hazard ratio, 5.57; 95% confidence interval, 2.28-13.57). Time-dependent changes in IFN-γ levels were significantly different between the recurrence and nonrecurrence groups (P < 0.0001).
  
  
  CONCLUSIONS
  Although the IGRA response varies individually, early response during the treatment course may provide an insight into host immune responses underlying tuberculosis recurrence.
authors: NCGM-BMH Medical Collaboration Center, 78 Giai Phong, Hanoi, Viet Nam.
authors: Nguyen Thi Le
authors: NT
authors: Hang
authors: Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan.
authors: Ikumi
authors: I
authors: Matsushita
authors: Clinical Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors: Takuro
authors: T
authors: Shimbo
authors: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam.
authors: Le Thi
authors: le T
authors: Hong
authors: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam.
authors: Do Bang
authors: do B
authors: Tam
authors: Hanoi Department of Health, 4 Son Tay, Hanoi, Viet Nam.
authors: Luu Thi
authors: LT
authors: Lien
authors: Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam.
authors: Pham Huu
authors: PH
authors: Thuong
authors: Hanoi Lung Hospital, 44 Thanh Nhan, Hanoi, Viet Nam.
authors: Vu Cao
authors: VC
authors: Cuong
authors: Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors: Minako
authors: M
authors: Hijikata
authors: NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan.
authors: Nobuyuki
authors: N
authors: Kobayashi
authors: Bureau of International Medical Cooperation, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors: Shinsaku
authors: S
authors: Sakurada
authors: Research Institute of Immune Diagnosis, 1-34-1 Fujimicho, Tachikawa, Tokyo 190-0013, Japan.
authors: Kazue
authors: K
authors: Higuchi
authors: Research Institute of Immune Diagnosis, 1-34-1 Fujimicho, Tachikawa, Tokyo 190-0013, Japan.
authors: Nobuyuki
authors: N
authors: Harada
authors: Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors: Hiroyoshi
authors: H
authors: Endo
authors: Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan; National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Electronic address: nkeicho-tky@umin.ac.jp.
authors: Naoto
authors: N
authors: Keicho
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000276:immunology*; D059425:Interferon-gamma Release Tests / Q000379:methods*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012008:Recurrence; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D053590:Interleukin 1 Receptor Antagonist Protein; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Cellular response; Interferon-γ release assay; Recurrence; Tuberculosis