The effect of anti-IL5 monoclonal antibodies on regulatory and effector T cells in severe eosinophilic asthma

Introduction: Biological treatments have redesigned the clinical management of severe eosinophilic asthmatic (SA) patients. Despite emerging evidence supporting the role of natural Killer (NK), and T regulatory cells (Treg) in the pathogenesis of asthma, no data is available on the effects of anti-IL5/IL5R therapies on these cell subsets.Methods: We prospectively enrolled fourteen SA patients treated with benralizumab (n = 7) or mepolizumab (n = 7) and compared them with healthy controls (HC) (n = 11) and mild to moderate asthmatic (MM) patients (n = 9). Clinical parameters were collected at baseline (T0) and during follow-up. Cellular analysis, including the analysis of T/NK cell subsets, was determined through multicolor flow cytometry.Results: At T0, SA patients showed higher percentages of CD4 TEM (33.3 +/- 17.9 HC, 42.6 +/- 16.6 MM and 66.1 +/- 19.7 in SA; p < 0.0001) than HC and MM patients. With different timing, the two drugs induce a reduction of CD4 TEM ( 76 +/- 19 T0; 43 +/- 14 T1; 45 +/- 23 T6; 62 +/- 18 at T24; p < 0.0001 for mepolizumab and 55 +/- 21 T0; 55 +/- 22 T1; 43 +/- 14 T6; 27 +/- 12 at T24; p < 0.0001 for benralizumab) and an increase of Treg cells (1.2 +/- 1.3 T0; 5.1 +/- 2.5 T1; 6.3 +/- 3.4 T6; 8.4 +/- 4.6 at T24; p < 0.0001 for mepolizumab and 3.4 +/- 1.7 T0; 1.9 +/- 0.8 T1; 1.9 +/- 1 T6; 5.1 +/- 2.4 at T24; p < 0.0001 for benralizumab). The change of CD56(dim) PD-1(+) significantly correlated with FEV1% (r = 0.32; p < 0.01), while Treg expressing PD-1 correlates with the use of oral steroids (r = 0.36 p = 0.0008) and ACT score (r = 0.36 p = 0.0008) p < 0.001)Conclusions: Beyond the clinical improvement, anti-IL-5 treatment induces a rebalancing of Treg and T effector cells in patients with SA