The effect of anti-IL5 monoclonal antibodies on regulatory and effector T cells in severe eosinophilic asthma
Laura Bergantini, Tommaso Pianigiani, Miriana d’Alessandro, Sara Gangi, Behar Cekorja, Elena Bargagli, Paolo Cameli
Abstract
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. 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. 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 CD56dim 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) Beyond the clinical improvement, anti-IL-5 treatment induces a rebalancing of Treg and T effector cells in patients with SA