Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis. (17th June 2019)

• Record Type: Journal Article
• Authors: Mavropoulos, Athanasios; Zafiriou, Efterpi; Simopoulou, Theodora; Brotis, Alexandros G; Liaskos, Christos; Roussaki-Schulze, Aggeliki; Katsiari, Christina G; Bogdanos, Dimitrios P; Sakkas, Lazaros I
• Is Part Of: Rheumatology. Volume 58:Number 12(2019)
• Page Start: 2240
• Page End: 2250
• Publication Date: 2019-06-17
• Subjects: spondylarthropathies -- psoriatic arthritis -- B-cells -- cytokines -- inflammatory mediators -- inflammation -- T cells; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/kez204
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives: Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL–10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. Methods: Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. Results: Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. Conclusion: These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.