The impact of mepolizumab therapy on Treg proliferation and exhaustion state

<bold>Background:</bold> mepolizumab is a humanized monoclonal antibody that binds circulating interleukin-5 (IL-5). T regulatory cells (Treg) are key regulators of immune homeostasis. PD-1 express on Treg cells contributing to exhaustion of these cell phenotypes. In severe asthma patients, decreased levels of Treg cells sustain the concept of immune effector and regulatory imbalance. In this research we evaluated the impact of mepolizumab treatment on Treg cells subsets and state of exhaustion in severe asthmatic patients (SA) treated with mepolizumab. <bold>Methods:</bold> We prospectively enrolled seven SA patients treated with mepolizumab, 11 healthy controls (HC) and 9 mild to moderate asthmatic (MM) patients. Clinical parameters were collected in a baseline (T0) and after 1 month, 6 and 24 months of therapy (T1, T6, T24). Blood samples were collected at the same timepoints. Treg cell subsets were determined through flow cytometry. <bold>Results:</bold> At T0, SA patients showed higher percentages of Treg cells than HC and MM patients. Mepolizumab treatment induced an increase of Treg and a reduced of PD-1 expression after 24 months of therapy. The change of PD-1+Treg significantly correlates with ACT score, ACQ score and use of oral steroids. <bold>Conclusions:</bold> Mepolizumab treatment induces a rebalancing of Treg cells activity and proliferation. This immunological effect contributes to the clinical efficacy of the drug.