Mepolizumab decreased the levels of serum galectin-10 and eosinophil cationic protein in asthma

Konomi Kobayashi; Hiroyuki Nagase; Naoya Sugimoto; Shiho Yamamoto; Akihiko Tanaka; Koichi Fukunaga; Ryo Atsuta; Etsuko Tagaya; Masayuki Hojo; Yasuhiro Gon; iPOT-5 Investigators

doi:10.5415/apallergy.2021.11.e31

Mepolizumab decreased the levels of serum galectin-10 and eosinophil cationic protein in asthma

Asia Pac Allergy. 2021 Jul 16;11(3):e31. doi: 10.5415/apallergy.2021.11.e31. eCollection 2021 Jul.

Authors

Affiliations

¹ Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
² Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
³ Division of Respiratory Medicine and Allergology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
⁴ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
⁵ Akihabara Atsuta Clinic, Tokyo, Japan.
⁶ Department of Respiratory Medicine, Tokyo Women's Medical University, Tokyo, Japan.
⁷ Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.

Abstract

Background: Mepolizumab, a humanized antibody targeting interleukin-5, decreases the number of blood eosinophils and the frequency of exacerbation of severe asthma. Galectin-10 is a protein within the cytoplasm of eosinophils and constitutes Charcot-Leyden crystals, which promotes key features of asthma. However, the relationship between time kinetics and clinical response of eosinophil-derived molecules such as galectin-10 or eosinophil cationic protein (ECP) has not been precisely investigated.

Objective: This study aimed to clarify the precise time course of the levels of serum galectin-10 and ECP after mepolizumab treatment and to analyze the relationship between the levels of eosinophil-derived molecules and the clinical background or response to mepolizumab treatment.

Methods: This multicenter, prospective open-label study recruited 20 patients with severe eosinophilic asthma. Mepolizumab was administered every 4 weeks for 32 weeks and the levels of various biomarkers were serially analyzed.

Results: The serum galectin-10 and ECP significantly and rapidly decreased 4 weeks after initial administration of mepolizumab. In contrast, basophil count, fractional exhaled nitric oxide, and the serum total IgE level were unchanged during treatment. Asthma Control Questionnaire-5, Asthma Health Questionnaire-33, and Lund-Mackay scores significantly improved after mepolizumab treatment. Both high ECP and eosinophil count related to better response in forced expiratory volume in 1 second (FEV₁) and measurable ECP level at 4 weeks after administration of mepolizumab related to the further improvement in FEV₁ toward week 32. No significant difference in improvement in FEV₁ was observed in galectin-10 high group. The level of ECP at baseline was significantly related to the higher prevalence of nasal polyp and Lund-Mackay score.

Conclusion: This study was the first to show that the levels of serum galectin-10 decreases after initial administration of mepolizumab. The significant relationship between serum ECP and better response in FEV₁ suggested the potential role of serum ECP as a predictive biomarker for the efficacy of mepolizumab (UMIN000030466).

Keywords: Asthma; Eosinophil cationic protein; Galectin-10; Interleukin-5; Mepolizumab.