Interleukin-5 receptor alpha (IL5RA), a subunit of the IL-5 receptor complex, plays a critical role in the signaling pathway of interleukin-5 (IL-5), a cytokine essential for the differentiation, survival, and activation of eosinophils. Expressed predominantly on eosinophils and basophils, IL5RA pairs with the common beta chain (βc) to form a functional receptor. Dysregulation of the IL-5/IL5RA axis is implicated in eosinophil-driven inflammatory diseases, such as severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and hypereosinophilic syndromes (HES).
IL5RA-targeted antibodies, a class of biologic therapies, are designed to disrupt this pathway by blocking IL-5 binding or depleting eosinophils via antibody-dependent cellular cytotoxicity (ADCC). Benralizumab, a humanized monoclonal antibody against IL5RA, exemplifies this approach by directly targeting the alpha subunit, leading to rapid eosinophil depletion. Compared to antibodies targeting IL-5 itself (e.g., mepolizumab), IL5RA antibodies may offer enhanced efficacy due to their dual mechanism of action.
Clinical trials have demonstrated that IL5RA antibodies reduce exacerbations, improve lung function, and decrease oral corticosteroid dependence in severe eosinophilic asthma. They also show promise in treating other eosinophilic disorders. By selectively modulating eosinophil activity, these therapies minimize systemic immunosuppression risks, offering a targeted strategy for managing chronic eosinophilic inflammation. Ongoing research explores broader applications, including eosinophilic gastrointestinal diseases and atopic dermatitis.