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Defect of Th1 immune response of whole blood cells from active patients with rheumatoid arthritis (RA)

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Cases of severe tuberculosis have been reported in patients with RA during anti-TNF-alpha (TNF-α) treatment. In addition to TNF-α, IFN gamma (IFN-γ) and the cellular immunity are known to be important to prevent the development of tuberculosis infection.

Objective and methods

We examined mRNA expression of IFN-γ, IL-4, T-bet, GATA-3, and TNF-α by peripheral whole blood from RA patients (n = 28) and healthy controls (n = 16), using real-time RT-PCR.


IFN-γ, IL-4, and TNF-α expression was significantly higher in RA than in healthy blood (P = 0.0023, 0.003, and 0.0004, respectively). In RA samples, T-bet expression correlated with that of IFN-γ (r = 0.738, P < 0.0001) and negatively correlated with serum CRP levels (r = -0.516, P = 0.004). No correlation between T-bet and IFN-γ expression was observed in healthy blood. Next, we separated RA patients into two groups according to their serum CRP levels. In comparison with healthy or mild RA (CRP <40 mg/l, n = 19), active RA blood (CRP >40 mg/l, n = 9) showed significantly lower ratio of T-bet/β-actin (P = 0.014, P = 0.0009) or T-bet/GATA-3 (P = 0.0035, P = 0.0085, respectively). Active RA blood expressed significantly lower IFN-γ mRNA in comparison with that of mild RA (P = 0.014). There was no difference of IFN-γ expression between active RA and healthy blood, but active RA showed higher expression of IL-4 than that of healthy samples (P = 0.025). TNF-α expression by active RA blood was lower than that of mild RA (P = 0.013) and healthy blood, though not significantly so.


These findings demonstrate that IFN-γ, T-bet, or TNF-α expression by whole blood cells may be influenced by disease activity of RA, and the combination of the defect of TNF-α and Th1 immune response indicated by low IFN-γ and T-bet with high IL-4 expression in the active RA blood, with the additional effect of blockade of TNF activation on T cells, may represent critical conditions for the development of tuberculosis.

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  • Rheumatoid Arthritis
  • Tuberculosis
  • Rheumatoid Arthritis Patient
  • Tuberculosis Infection
  • Active Rheumatoid Arthritis