The effects of rituximab therapy on released interferon-γ levels in the QuantiFERON assay among RA patients with different status of Mycobacterium tuberculosis infection

Rheumatology (Oxford). 2013 Apr;52(4):697-704. doi: 10.1093/rheumatology/kes365. Epub 2012 Dec 22.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • B-Lymphocytes / drug effects
  • C-Reactive Protein / metabolism
  • Female
  • Humans
  • Interferon-gamma / blood*
  • Interferon-gamma Release Tests
  • Latent Tuberculosis / diagnosis
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Rheumatoid Factor / blood
  • Rituximab
  • Severity of Illness Index
  • T-Lymphocytes / drug effects
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Interferon-gamma
  • C-Reactive Protein
  • Rheumatoid Factor