OP0273 Tocilizumab Enhances Regulatory T Cell Activation and Proliferation in Giant Cell Arteritis
Authors: C. Miyabe, K. Strle, Y. Miyabe, J.H. Stone, A.D. Luster, S. Unizony
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Both CD4<sup>+</sup> T helper (Th)-type 17 lymphocytes and Th1-type lymphocytes appear to contribute to the pathogenesis of giant cell arteritis (GCA). In addition, regulatory T cell (Treg) responses appear to be suppressed in GCA. Interleukin (IL)-6, highly expressed in GCA patients, is a key mediator in the differentiation of both Th17 and Treg cells. Preliminary experience in GCA with the use of tocilizumab (TCZ), an IL-6 receptor antagonist, has been encouraging. However, it is unknown whether TCZ affects the differentiation and function of these CD4<sup>+</sup> T-cell subsets in these patients. <h3>Objectives</h3> We aimed to characterize the effector and regulatory CD4<sup>+</sup> T-cell compartments in the peripheral blood of GCA patients treated with TCZ. <h3>Methods</h3> We evaluated 38 GCA patients classified into one of three categories: 1) active disease (aGCA, n=9); 2) disease remission on corticosteroid (CS) monotherapy (rGCA-CS, n=18); and 3) disease remission on TCZ therapy (rGCA-TCZ, n=11). Nine healthy controls were also included. Using flow cytometry, we determined the percentages (%) of IFNg<sup>+</sup>IL-17<sup>-</sup> (Th1), IL-17<sup>+</sup>IFNg<sup>-</sup> (Th17), CD25<sup>high</sup> (Treg), and CD45RA<sup>-</sup>Foxp3<sup>high</sup> (activated Treg, aTreg) cells within the CD4<sup>+</sup> lymphocyte population. In addition, we determined the % of Foxp3<sup>+</sup> cells expressing Ki67 (proliferating Treg). We assessed Treg function in suppression assays. Serum concentrations of IL-12, IFNg, IL-6, IL-1β, IL-23, IL-21, TNF-α, CCL20, IL-17A, and IL-10 were measured by Luminex. <h3>Results</h3> The frequencies (mean %) of Th1, Th17, and Treg cells were equivalent across groups. However, the frequency of aTregs was higher in rGCA-TCZ patients (1.3%) compared with rGCA-CS patients (0.6%; p=0.02). Moreover, the number of proliferating Tregs was significantly higher in rGCA-TCZ patients (31.7%) compared to rGCA-CS (16.4%; p=0.003) and aGCA (15.5%; p=0.007) patients. Tregs were functional in all groups. IL-10 levels were significantly increased in the serum of patients with aGCA. There were no significant differences in the serum levels of other cytokines or chemokines measured. <h3>Conclusions</h3> The therapeutic effects of tocilizumab in GCA could be mediated by increasing the activation and proliferative potential of Tregs. Further studies are needed to expand these preliminary findings. <h3>References</h3> Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012; 64(11): 1720-9. Osman M, Pagnoux C, Dryden DM, Storie D, Yacyshyn E. The Role of Biological Agents in the Management of Large Vessel Vasculitis (LVV): A Systematic Review and Meta-Analysis. PLoS One. 2014;9(12):e115026. <h3>Disclosure of Interest</h3> None declared