Anti-inflammatory effects of oral prednisolone at stable state in people treated with mepolizumab: a proteomic and bulk transcriptomics analysis

• DOI: 10.1101/2024.02.14.24302812
• Publication Date: 2024-02-15T22:00:15Z
• Authors: I. Howell; F. Yang; V. Brown; J. Cane; E. Marchi; A Azim; J. Busby; P.J. McDowell; S.E. Diver; C. Borg; L. G. Heaney; I. D. Pavord; C. E. Brightling; R. Chaudhuri; T.S.C. Hinks
• Keywords: Prednisolone; Eosinophil peroxidase; Eosinophilic Esophagitis; Fluticasone

Abstract Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces exacerbations. Residual airway inflammation on mepolizumab may lead to persistent Oral corticosteroids have broad anti-inflammatory effects and remain the main these residual Our study aimed explore nature corticosteroid-responsiveness of after find potentially treatable inflammatory mechanisms. The MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover 2 weeks high-dose oral prednisolone at stable state in patients treated with SEA. We analysed sputum plasma samples from using high-throughput Olink® proteomics. also microRNA, proteins ELISA, nasal mucosal bulk RNA sequencing. In receiving mepolizumab, significantly downregulated related type-2 chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, ST2 receptor. Prednisolone cell adhesion molecules, prostaglandin synthases, mast tryptases, MMP1, MMP12, neuroimmune mediators. Tissue repair neutrophilic pathways were upregulated. Type-2 plasma, combined IL-12, IFN-γ, IP-10. IL-10 amphiregulin transcriptome, suppressed genes involved leucocyte chemotaxis, tryptase, 15-lipoxygenase MMP12 . By contrast, differentially regulated only Galectin-10 no proteins, tissue affected cilia, keratinisation, extracellular matrix formation, IL-4/13 signalling. At state, has top mepolizumab. Graphical abstract