Macrophage requirements for abatacept response in rheumatoid arthritis

Objective 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-gamma. This inhibitory effect of ABA was abolished by blockade of IDO. Conclusion 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.