Apremilast therapy increases CD39+CD4+ T cells in peripheral blood of patients with psoriatic disease: a retrospective observational pilot study.

Psoriasis and psoriatic arthritis (PsA) are chronic inflammatory diseases, recognized as one entity, termed psoriatic disease (PsD). CD39 is an ectonucleotidase that hydrolyzes ATP to adenosine and is expressed on a human Treg sub-population capable of exerting interleukin (IL-) 17 suppression. We aimed to investigate the effect of apremilast on CD39 expression in T cells from patients with PsD. Peripheral blood mononuclear cells (PBMCs) were analyzed by multicolor flow cytometry and appropriate monoclonal antibodies. Intracellular cytokine production of PBMCs was measured after in vitro PMA plus ionomycin stimulation. At 6 weeks post-treatment, apremilast inhibited IL-17 and interferon-γ (IFNγ) production, increased IL-10 production in both CD4+T cells and CD4-T cells, and inhibited IL-6 production in CD4-T cells. At baseline, levels of CD4+CD39+ cells were decreased in patients compared to controls. At 6 weeks post-treatment, CD4+CD39+ cells increased. Furthermore, CD4+CD39+ cells producing IL-10 increased in patients who achieved a PASI response. A significant proportion of IL-10-producing CD39+ cells were CD56-CD11c- cells. CD4+FoxP3+ cells were decreased in patients compared to controls. At 6 weeks post-treatment CD4+FoxP3+ cells, and CD4+FoxP3+CD39+ cells increased, although CD4+CD25hiFoxP3+ Treg cells did not change significantly. If confirmed in larger studies, CD4+CD39+ cells producing IL-10 could likely become associated with the response to apremilast.