title: The effects of rituximab therapy on released interferon-γ levels in the QuantiFERON assay among RA patients with different status of Mycobacterium tuberculosis infection.
abstract: OBJECTIVE
  To investigate the influence of rituximab therapy on released IFN-γ levels in the QuantiFERON-TB-Gold In-Tube (QFT-GIT) assay among RA patients of different Mycobacterium tuberculosis infection status.
  
  
  METHODS
  Change in levels of released IFN-γ in the QFT-GIT assay was evaluated in RA patients who had received 1 year of rituximab treatment. A tuberculin skin test was performed using the Mantoux method and the QFT-GIT assay was performed by measuring IFN-γ levels in whole blood treated with tuberculosis (TB)-specific antigens.
  
  
  RESULTS
  Among 56 patients, 43 patients were presumed to be without latent TB infection (LTBI), 7 patients had LTBI and 6 patients had anti-TNF-associated TB. During the 1-year period of rituximab therapy, no patient developed active TB or had QFT-GIT conversion. No significant change in released IFN-γ levels on QFT-GIT assay after 1-year rituximab therapy was observed in patients with LTBI [3.39 (1.21) vs 2.47 (0.82) IU/ml] or in those with anti-TNF-associated TB [1.06 (0.22) vs 0.87 (0.39) IU/ml]. Rituximab did not inhibit TB antigen-stimulated IFN-γ production ex vivo. The frequency of circulating CD19(+) B cells was significantly decreased [8.56 (0.84) vs 1.52 (0.44)%, P < 0.001], paralleling the decrease in RF titre [318.5 (76.0) vs 115.1 (32.1) IU/ml, P < 0.001] and DAS28 [6.49 (0.13) vs 4.59 (0.14), P < 0.001] after 1 year of rituximab therapy. However, there was no significant change in the frequency of CD3(+) T cells after rituximab therapy.
  
  
  CONCLUSIONS
  No occurrence of active TB or QFT-GIT conversion was observed in patients receiving 1 year of rituximab therapy. No significant effect of rituximab therapy on IFN-γ release levels was observed in patients with LTBI and with anti-TNF-α-associated TB. Rituximab may be an alternative therapeutic agent for these patients.
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.forename: Kuo-Lung
authors.initials: KL
authors.lastname: Lai
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D007371:Interferon-gamma; D002097:C-Reactive Protein; D012217:Rheumatoid Factor