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FRI0504 Apremilast expands IL-10-producing regulatory b cells, and decreases TH1 and TH7 cells in psoriatic arthritis and psoriasis
  1. A Mavropoulos1,
  2. E Zafiriou2,
  3. A Varna1,
  4. E Papadopoulou2,
  5. I Alexiou1,
  6. A-V Roussaki-Schulze2,
  7. DP Bogdanos1,
  8. LI Sakkas1
  1. 1Rheumatology and Clinical Immunology
  2. 2Dermatology, University of Thessaly, School of Health Sciences, LARISSA, Greece

Abstract

Background IL-10-producing regulatory B cells (Bregs), also known as B10 cells, are decreased and inversely correlate with IFN-γ- and IL-17-producing NK and T cells in patients with psoriatic arthritis (PsA) and psoriasis (Ps) (1–3)

Objectives To assess whether or not apremilast, a PDE4 inhibitor recently approved for the treatment of Ps and PsA, is able to induce IL-10-producing B cells and decrease Th1 cells and Th17 cells in vivo

Methods PBMCs and magnetically purified B cells were isolated from 21 patients (7 PsA, all responders; 14 Ps, 9 responders) at baseline and post-apremilast treatment (at 3 and 6 months in responders; at 3 months in non–responders, as they switched to biologicals). Phenotypic analysis of CD3, CD19, CD24, CD27, CD38 and intracellular expression of cytoplasmic IL-10, IFN-γ, IL-17 after bacterial CpG (ODN2006) and PMA/ionomycin stimulation was examined by flow cytometry

Results At 6 months, apremilast significantly increased IL-10-producing Bregs (IL-10+CD19+, B10 cells) compared to baseline and 3 months. B10 cells increase was confined mainly to the transitional Bregs (CD19+CD24highCD38high) rather than memory Bregs (CD19+CD27+CD24high). IFNγ+CD3+ (Th1) and IL-17+CD3+ (Th17) T cells were significantly decreased at 3 and 6 months (p<0.05, for both). There was an inverse correlation between percentages of B10 cells and IFN-γ-producing CD3+ cells. The percentage of B10 cells were not changed post-treatemnt in non-responders.

Conclusions Our data suggest that apremilast may exert its therapeutic effect through the expansion of IL-10-producing Bregs and the decrease of IFN-γ- and/or IL-17-producing T cells

References

  1. Mavropoulos et al Ann Rheum Dis 2015;74 Suppl 2 423.

  2. Mavropoulos et al Ann Rheum Dis 2016;75 Suppl 2 903.

  3. Mavropoulos et al Arthritis Rheumatol. 2016; 68 (suppl 10).

References

Disclosure of Interest None declared

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