Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.

Objectives: To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab.
Methods: Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab ( n  = 20) or glucocorticoids ( n  = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T-cell (Teff) proliferation and polarisation into Th1 and Th17 cells.
Results: Treg (CD4 ⁺ CD25 ^high FoxP3 ⁺ ) frequency in total CD4 ⁺ T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P  < 0.001) and increased after treatment with tocilizumab but worsened after treatment with glucocorticoids alone. Treg lacking exon 2 of FoxP3 were increased in GCA patients when compared to controls (23% vs. 10% of total Treg, P  = 0.0096) and normalised after treatment with tocilizumab + glucocorticoids but not glucocorticoids alone. In GCA patients, Treg were unable to control Teff proliferation and induced ˜50% increase in the amount of IL-17 ⁺ Teff, which was improved after in vitro blockade of the IL-6 pathway by tocilizumab.
Conclusion: This study reports quantitative and functional disruptions in the regulatory immune response of GCA patients and demonstrates that, unlike glucocorticoids, tocilizumab improves Treg immune response.
Competing Interests: Maxime Samson has received travel fees and personnel fees for symposium and boards from Roche–Chugaï, and consulting fees from AbbVie. Bernard Bonnotte serves as a board member for Roche–Chugaï. Catherine CREUZOT‐GARCHER has received a grant from Horus and Bayer, honoraria from Novartis and Bayer and serves as a medical advisory board member for Novartis, Bayer, Thea, Horus, Alcon and Allergan. Pierre‐Henry Gabrielle has received travel expenses from Allergan, Bayer and Novartis, and honoraria from Novartis and Bayer.
(© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)