We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact us so we can address the problem.
Defect of Th1 immune response of whole blood cells from active patients with rheumatoid arthritis (RA)
© The Author(s) 2003
- Received: 14 January 2003
- Published: 24 February 2003
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Tuberculosis Infection
- Active Rheumatoid Arthritis
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.
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.