The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis.

BACKGROUND: The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not unanimously accepted, several reports have shown that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effects of ABT and TCZ on the skewing of T cell populations, we analyzed the expression of master regulators genes of helper T cell lineages following ABT/TCZ treatment of RA patients. METHODS: Ten patients treated with ABT and 10 patients treated with TCZ were enrolled. Total RNA was extracted from peripheral blood cells at baseline, and after 12 and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were semi-quantified using real-time PCR. The relative expression levels were expressed as the ratios of two genes (T-bet/GATA3, Foxp3/GATA3, Foxp3/T-bet, Foxp3/Ror-γt, Ror-γt/T-bet, Ror-γt/GATA3), and the changes in these ratios with treatment were determined. RESULTS: The Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 at 24 weeks, P = 0.0034) but was increased after TCZ therapy (2.00 ± 1.03 at 24 weeks, P = 0.0013). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.37 at 24 weeks, P = 0.0008). Except for these ratios, no significant skewing in the expression of these factors was detected. No significant relationship between clinical response to the treatment and change in the ratios of these factors was determined. CONCLUSION: Treatment with TCZ or ABT differently affected the balance between Foxp3 and Ror-γt expression in the peripheral blood of patients with RA.

Effectiveness of Certolizumab Pegol in Treating Rheumatoid Arthritis Patients with Persistent Inflamed Residual Mono- or Oligosynovitis Resistant to Prior TNF-α Inhibitors.

We report four cases of successful treatment with certolizumab pegol (CZP) of rheumatoid arthritis (RA) patients with persistent inflamed residual mono- or oligosynovitis resistant to prior TNF-α inhibitors. Although the patients were in a moderate disease activity, a low activity, or a remission of RA, they sustained inflammatory mono-/oligoarthritis even after treatment with prior TNF inhibitors. They were then all treated with CZP and observed in a serial ultrasonography. In all cases, the positive power Doppler signals in the joint have disappeared promptly and all of the patients were able to retain remission in the long term. The treatment of CZP to the refractory mono-/oligoarthritis of inflammatory synovitis in RA patients has not been previously described. The cases suggest that it may be associated with the feature of CZP, possible effective penetration into the site of inflammation.