Full Papers
Macrophage requirements for abatacept response in rheumatoid arthritis
B. De Maleprade1, B. Gérard2, P. Brevet3, G. Riou4, S. Candon5, O. Boyer6, O. Vittecoq7, T. Lequerré8, M. Fréret9
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Immunology and Biotherapies, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Immunology and Biotherapies, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France.
- Department of Rheumatology & CIC-CRB 1404, CHU Rouen, Université Rouen Normandie, Inserm, Normandie Université, PANTHER UMR 1234, Rouen, France. manuel.freret@inserm.fr
CER18199
2025 Vol.43, N°5
PI 0874, PF 0879
Full Papers
PMID: 40242906 [PubMed]
Received: 30/09/2024
Accepted : 13/01/2025
In Press: 09/04/2025
Published: 08/05/2025
Abstract
OBJECTIVES:
Abatacept (ABA) is used for its ability to dampen T cell co-stimulation and because it could act on antigen-presenting cells in an indoleamine 2,3-dioxygenase (IDO)-dependent manner. The objective of this study was to identify biomarkers of ABA response in rheumatoid arthritis (RA) patients and to determine the involvement of IDO.
METHODS:
RA patients’ samples were collected before and after ABA treatment. Clinical response was assessed after 6 months, macrophage phenotype was assessed by flow cytometry. IDO transcript expression were quantified in blood cells by RT-qPCR. In vitro assay: GM-CSF or M-CSF monocyte-derived macrophages from healthy donors were polarised with LPS, with or without IFN-g, and co-cultured with T cells in the presence of anti-CD3, with or without ABA. Macrophage phenotype and T cell proliferation were assessed.
RESULTS:
In RA patients, the frequency of CD16- CD64+ CD86high macrophages pre-treatment was increase in ABA good responders compared to non-responders. ABA seemed to increase IDO production. In vitro, ABA reduced the proliferation of T cells activated by anti-CD3 and macrophages differentiated and polarised with GM-CSF+LPS+IFN-γ. This inhibitory effect of ABA was abolished by blockade of IDO.
CONCLUSIONS:
ABA response in RA patients is associated with a particular pro-inflammatory macrophage phenotype pre-treatment and IDO is required for ABA effect. These findings reveal predictive markers of ABA response and the involvement of the IDO pathway.
