Open AccessImprovement of Treg immune response after treatment with tocilizumab in giant cell arteritis
Author(s) -
Samson Maxime,
Greigert Hélène,
Ciudad Marion,
Gerard Claire,
Ghesquière Thibault,
Trad Malika,
CorberaBellalta Marc,
Genet Coraline,
Ouandji Sethi,
Cladière Claudie,
Thebault Marine,
Ly Kim Heang,
Liozon Eric,
Maurier François,
Bienvenu Boris,
Terrier Benjamin,
Guillevin Loïc,
Charles Pierre,
Quipourt Valérie,
Devilliers Hervé,
Gabrielle PierreHenry,
CreuzotGarcher Catherine,
Tarris Georges,
Martin Laurent,
Saas Philippe,
Audia Sylvain,
Cid Maria Cinta,
Bonnotte Bernard
Publication year - 2021
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1332
Subject(s) - tocilizumab , giant cell arteritis , immune system , foxp3 , immunology , flow cytometry , immune dysregulation , medicine , glucocorticoid , interleukin 6 , inflammation , vasculitis , rheumatoid arthritis , disease
Abstract 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.