托珠单抗治疗巨细胞动脉炎后调节性T细胞免疫反应的改善
Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.
作者信息
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
机构信息
Department of Internal Medicine and Clinical Immunology Dijon University Hospital Dijon France.
Université Bourgogne Franche-Comté INSERM EFS BFC UMR1098 RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique Dijon France.
出版信息
Clin Transl Immunology. 2021 Sep 12;10(9):e1332. doi: 10.1002/cti2.1332. eCollection 2021.
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 ( = 20) or glucocorticoids ( = 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 (CD4CD25FoxP3) frequency in total CD4 T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, < 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, = 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 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.
目的
研究巨细胞动脉炎（GCA）中调节性T细胞（Treg）的百分比、抑制功能和可塑性，以及糖皮质激素和托珠单抗的作用。
方法
在基线时以及使用糖皮质激素联合静脉注射托珠单抗（n = 20）或糖皮质激素（n = 23）治疗后，从40名对照者和43名GCA患者中采集血样。通过流式细胞术评估Treg百分比和表型。通过测量Treg抑制效应T细胞（Teff）增殖以及向Th1和Th17细胞极化的能力来评估Treg的抑制功能。
结果
与对照者相比，活动期GCA患者总CD4 T细胞中Treg（CD4⁺CD25⁺FoxP3⁺）频率降低（2.5%对4.7%，P < 0.001），托珠单抗治疗后升高，但单独使用糖皮质激素治疗后恶化。与对照者相比，GCA患者中缺乏FoxP3外显子2的Treg增加（占总Treg的23%对10%，P = 0.0096），托珠单抗联合糖皮质激素治疗后恢复正常，但单独使用糖皮质激素则未恢复正常。在GCA患者中，Treg无法控制Teff增殖，且使IL-17⁺ Teff的量增加约50%，托珠单抗阻断IL-6途径后有所改善。
结论
本研究报告了GCA患者调节性免疫反应的定量和功能破坏，并表明与糖皮质激素不同，托珠单抗可改善Treg免疫反应。
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