oa Molecular Diagnosis and Vaccines - Th1 and Th2 cytokine production at the level of transcriptional regulation in the peripheral blood from rheumatoid arthritis patients
T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) are transcriptional factors that play a crucial role in Th1 and Th2 development. We investigated the immunomodulatory roles of T-bet and GATA-3 and Th1/Th2 related cytokines IFN-? and IL-4 in the pathogenesis of rheumatoid arthritis (RA) and their association with disease activity. The mRNA markers level was measured in the peripheral blood of RA patients and controls by real-time PCR. Total RNA was isolated directly from peripheral blood of 21 RA patients and 10 healthy controls. The mRNA levels of T-bet, IFN-? and IFN-?/IL-4 ratio were significantly lower in RA patients than controls (p= 0.001, p= 0.000, p=0.014 respectively). In all RA patients, there were significant positive correlations in mRNA expression of T-bet with IFN-? (r =0.895, p= 0.000), and of GATA-3 with IL-4 (r =0.089, P =0.000). RA patients were divided into two groups according to C reactive protein (CRP) levels. In comparison to RA patients with a low positive CRP (CRP < 12 mg/L), patients with a high positive CRP (CRP ? 12 mg/L) had lower T-bet, IFN-? expression as well as IFN-?/IL-4 and T-bet/GATA-3 expression ratios. Conversely, the mRNA expression of GATA-3 and IL-4 increased in the low positive CRP group compared to the high positive CRP group but it did not reach a significant value (p =0.204, p =0.259 respectively). In conclusion, this study demonstrates that peripheral blood from RA patients showed a decreased Th1 response as indicated by low T-bet and IFN- ? mRNA expression, which was found mainly in patients with the most active disease. The suppressed function of Th1, associated with the suppression of both T-bet and IFN-? gene expression, may be one of the immunological characteristics of rheumatoid arthritis.
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