Background/Purpose: It has been shown that the balance between Th17 cells and regulatory T (Treg) cells plays an important role for the development of autoimmune diseases including rheumatoid arthritis (RA). Th17 cells secrete IL-17 and generally promote autoimmunity, whereas Treg cells interact with a various cells and regulate autoimmunity and inflammation. Recent studies showed that the treatment with abatacept (ABT) or tocilizumab (TCZ) affected the population of Th17 cells and Treg cells in patients with RA. Although not unanimously approved, several reports showed that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effect of ABT and TCZ on the skewing of T cells, we analyzed the expression of master regulators of helper T cell lineages, in patients with RA treated with ABT or TCZ.

Methods: Ten patients treated with ABT and 9 patients treated with TCZ were enrolled. All patients met the 2010 ACR/EULAR classification criteria. Total RNA was extracted from peripheral blood cells at baseline, and after 12 weeks and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were measured by real-time PCR using Light Cycler 480. Because of different T cell counts in each sample, 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 (the ratios at baseline were defined as 1.00) were determined. This study was approved by the local ethics committee, and written informed consent was obtained from all patients.

Results: In patients treated with ABT, the mean DAS28CRP was 3.92 before treatment, and 5 patients achieved remission or low disease activity, whereas in patients treated with TCZ, the mean CDAI was 14.7 before treatment, and 8 patients achieved remission. The Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 (0.33 to 0.91) at 24 weeks, p=0.0034), but was increased after TCZ therapy (2.00 ± 1.03 (0.63 to 3.47) at 24 weeks, p=0.0035). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.39 (0.29 to 1.70) at 24 weeks, p=0.0029). Except for these, no significant skewing was observed. No significant relationships between clinical response to the treatment and the changes in the ratios were detected.

Conclusion: The treatment with TCZ or ABT differently affected the balance of Foxp3/Ror-γt expression in the peripheral blood of patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-balance-of-foxp3ror-gammat-expression-is-altered-by-tocilizumab-and-by-abatacept-in-patients-with-rheumatoid-arthritis/