Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis
Maxime Samson
(1, 2)
,
Hélène Greigert
(1, 2)
,
Marion Ciudad
(2)
,
Claire Gerard
(2)
,
Thibault Ghesquière
(1, 2)
,
Malika Trad
(2)
,
Marc Corbera-Bellalta
(3, 4)
,
Coraline Genet
(2)
,
Sethi Ouandji
(2)
,
Claudie Cladière
(2)
,
Marine Thébault
(2)
,
Kim Heang Ly
(5)
,
Eric Liozon
(5)
,
François Maurier
(6)
,
Boris Bienvenu
(7)
,
Benjamin Terrier
(8)
,
Loïc Guillevin
(8)
,
Pierre Charles
(9)
,
Valérie Quipourt
(1)
,
Hervé Devilliers
(1, 10)
,
Pierre-Henry Gabrielle
(11)
,
Catherine Creuzot-Garcher
(11)
,
Georges Tarris
(1)
,
Laurent Martin
(1)
,
Philippe Saas
(2, 12)
,
Sylvain Audia
(1, 2)
,
Maria Cinta Cid
(13, 4)
,
Bernard Bonnotte
(1, 2)
1
CHU Dijon -
Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
2 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
3 Hospital Clínic de Barcelona
4 University of Barcelona
5 CHU Limoges
6 HPMetz - Hôpitaux Privés de Metz
7 Hôpital Saint-Joseph [Marseille]
8 Hôpital Cochin [AP-HP]
9 IMM - Institut Mutualiste de Montsouris
10 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques
11 Service d'Ophtalmologie (CHU de Dijon)
12 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
13 Hospital Clínic de Barcelona
2 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
3 Hospital Clínic de Barcelona
4 University of Barcelona
5 CHU Limoges
6 HPMetz - Hôpitaux Privés de Metz
7 Hôpital Saint-Joseph [Marseille]
8 Hôpital Cochin [AP-HP]
9 IMM - Institut Mutualiste de Montsouris
10 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques
11 Service d'Ophtalmologie (CHU de Dijon)
12 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
13 Hospital Clínic de Barcelona
Maxime Samson
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- Fonction : Auteur correspondant
- PersonId : 1077020
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Benjamin Terrier
- Fonction : Auteur
- PersonId : 762205
- ORCID : 0000-0001-6612-7336
- IdRef : 13141142X
Pierre-Henry Gabrielle
- Fonction : Auteur
- PersonId : 783994
- ORCID : 0000-0002-9688-4845
Catherine Creuzot-Garcher
- Fonction : Auteur
- PersonId : 760739
- ORCID : 0000-0002-3587-4598
Laurent Martin
- Fonction : Auteur
- PersonId : 921720
Sylvain Audia
- Fonction : Auteur
- PersonId : 763846
- IdHAL : sylvain-audia
- ORCID : 0000-0003-1772-1392
- IdRef : 128667648
Résumé
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.