Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.
Clin Transl Immunology
; 10(9): e1332, 2021.
Article
em En
| MEDLINE
| ID: mdl-34532040
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+CD25highFoxP3+) 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 Ë50% 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.
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MEDLINE
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Ano de publicação:
2021
Tipo de documento:
Article