PT -期刊文章盟Van Hulst Glenn盟——乔rssen, Joseph AU - Jacobs, Nathalie AU - Henket, Monique AU - Louis, Renaud AU - Schleich, Florence AU - Bureau, Fabrice AU - Desmet, Christophe J. TI - Anti-IL-5 mepolizumab minimally influences residual blood eosinophils in severe asthma AID - 10.1183/13993003.00935-2021 DP - 2021 Jan 01 TA - European Respiratory Journal PG - 2100935 4099 - //www.qdcxjkg.com/content/early/2021/07/29/13993003.00935-2021.short 4100 - //www.qdcxjkg.com/content/early/2021/07/29/13993003.00935-2021.full AB - Neutralising antibodies against the cytokine interleukin (IL)-5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression program of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Glenn Van Hulst has nothing to disclose.Conflict of interest: J. Jorssen reports PhD student scholarship from Fonds de la Recherche scientifique (FRS)-FNRS (Belgium).Conflict of interest: N. Jacobs reports consulting fees and lecture fees from GSK, outside the submitted work.Conflict of interest: Monique Henket has nothing to disclose.Conflict of interest: L. Renaud reports grants from GSK, AZ, Novartis, Chiesi and Teva; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees and lecture payments from GSK, AZ, Novartis, Sanofi and Chiesi, outside the submitted work.Conflict of interest: F. Schleich reports grants from GSK, Astrazeneca, Teva, Chiesi and Novartis; consulting fees from GSK, Astrazeneca, Amgen, Chiesi and Novartis; lecture payments from GSK, Astrazeneca, Teva, Chiesi and Novartis, outside the submitted work.Conflict of interest: Fabrice Bureau has nothing to disclose.Conflict of interest: C. Desmet reports salary from Fonds de la Reherche Scientifique – FNRS (Belgium), during the submitted work; consulting fees in Advisory Board on eosinophil research from AstraZeneca; lecture fees for presentation at several scientific symposia in Europe on our research on eosinophils from GSK, outside the submitted work.