Abstract
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 programme 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.
Abstract
Asthma patients receiving anti-IL5 therapies retain residual blood eosinophils, of which potential alterations remain unknown. This study shows that these residual eosinophils harbour largely unaltered quiescent and activated gene expression programmes. https://bit.ly/37od6QN
Footnotes
Conflict of interest: G. 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: M. Henket has nothing to disclose.
Conflict of interest: R. Louis 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: F. Bureau has nothing to disclose.
Conflict of interest: C.J. Desmet reports salary from Fonds de la Reherche Scientifique – FNRS (Belgium), during the submitted work; consulting fees from AstraZeneca; lecture fees for presentation at several scientific symposia from GSK, outside the submitted work.
Support statement: This work was supported by the Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO) and the Fonds de la Recherche Scientifique (FRS) – FNRS (Belgium) under EOS project number 30565447 (U-HEAD), by a research project grant (T.0052.18 REGEOS) of the FRS-FNRS, by the Leon Fredericq Foundation (Liege University), and by Liege University. J. Jorssen is a doctoral research fellow, and C.J. Desmet is a research associate of the FRS-FNRS. Funding sources were not involved in the research. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received March 30, 2021.
- Accepted July 30, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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