Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis. Issue 9 (12th September 2021)

• Record Type: Journal Article
• Authors: Samson, Maxime; Greigert, Hélène; Ciudad, Marion; Gerard, Claire; Ghesquière, Thibault; Trad, Malika; Corbera‐Bellalta, 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, Pierre‐Henry; Creuzot‐Garcher, Catherine; Tarris, Georges; Martin, Laurent; Saas, Philippe; Audia, Sylvain; Cid, Maria Cinta; Bonnotte, Bernard
• Is Part Of: Clinical & translational immunology. Volume 10:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-12
• Subjects: giant cell arteritis -- interleukin‐6 -- tocilizumab -- Treg; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1332
• Languages: English
• ISSNs: 2050-0068

Abstract

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. Abstract : In this study, we demonstrated quantitative and functional disruptions in the regulatory immune response of patients with giant cell arteritis, resulting in increased proliferation and Th17 polarization of effector T cells. In addition, our results suggest that, through a specific blockade of the IL‐6 pathway, tocilizumab associated with glucocorticoids restores a better quantitative and qualitative Treg immune response than glucocorticoids alone. GCA, giant cell arteritis. Teff, effector T‐cells; Th17, T helper‐17 cells; Treg, regulatory T‐cells.