Benralizumab Restored Expression Of Key Molecules Involved In Steroid-Resistance In Patients With Severe Asthma

Background: Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, has been shown to allow reduced oral steroid dosage in patients with severe asthma. This result suggests that benralizumab may modify the function of molecules involved in the steroid response. This hypothesis is yet to be validated. Aims: To assess the expression levels of gene involved in the mechanism of steroid resistance, and to investigate the relationships between changes in gene expression and lung function, in patients undergoing benralizumab treatment. Methods: All subjects were administered benralizumab (30 mg) at weeks 0 (baseline), 4, 8, 16, and 24. Blood samples were collected prior to each administration until week 24. T cells were immediately separated from whole blood, and their total RNA was extracted. Results: Subjects included 17 patients with severe asthma. mRNA expression levels of histone deacetylase 2 (HDAC2), nuclear factor, erythroid 2 like 2 (Nrf2), glucocorticoid induced 1 (GLCCI1), and phosphatase and tensin homolog (PTEN), involved in the phosphoinositide 3-kinase pathway, tended to increase at week 8 and were significantly increased at weeks 16 and 24 (at week 24; HDAC2, p = 0.011; Nrf2, p = 0.015; GLCCI1, p = 0.020; PTEN, p = 0.027). Changes in expression levels of HDAC2, Nrf2, and GLCCI1, but not PTEN, from baseline to week 24 correlated significantly with changes in FEV1 (HDAC2, r = 0.67; Nrf2, r = 0.62; GLCCI1, r = 0.67). Conclusions: We demonstrated that changes in expression levels of genes involved in steroid resistance were associated with increased FEV1 after benralizumab treatment. Our results may help to understand the pathophysiology of severe asthma.