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  • Winslow, S. (author)

Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-03-25
  • European Respiratory Society (ERS),2021

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/310430
  • https://gup.ub.gu.se/publication/310430URI
  • https://doi.org/10.1183/13993003.03312-2020DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS in the airways and the phenotypic characteristic of patients with increased IL-6TS pathway activation remain poorly understood. Objective: Our aim was to identify and characterise COPD patients with increased airway IL-6TS and to elucidate the biological drivers of IL-6TS pathway activation. Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL1 beta, IL-8, macrophage inflammatory protein-1 beta) to stratify sputum data from patients with COPD (n=74; Biomarkers to Target Antibiotic and Systemic Corticosteroid Therapy in COPD Exacerbation (BEAT-COPD)) by hierarchical clustering. The IL-6TS signature was related to clinical characteristics and sputum microbiome profiles. The induction of neutrophil extracellular trap formation (NETosis) and IL-6TS by Haemophilus influenzae were studied in human neutrophils. Results: Hierarchical clustering revealed an IL-6TS-high subset (n=24) of COPD patients, who shared phenotypic traits with an IL-6TS-high subset previously identified in asthma. The subset was characterised by increased sputum cell counts (p=0.0001), persistent sputum neutrophilia (p=0.0004), reduced quality of life (Chronic Respiratory Questionnaire total score; p=0.008), and increased levels of pro-inflammatory mediators and matrix metalloproteinases in sputum. IL-6TS-high COPD patients showed an increase in Proteobacteria, with Haemophilus as the dominating genus. NETosis induced by H. influenzae was identified as a potential mechanism for increased sIL-6R levels. This was supported by a significant positive correlation between sIL-6R and NETosis markers in bronchoalveolar lavage fluid from COPD patients. Conclusion: IL-6TS pathway activation due to chronic colonisation with Haemophilus may be an important disease driver in a subset of COPD patients.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Odqvist, L. (author)
  • Diver, S. (author)
  • Riise, R. (author)
  • Abdillahi, S. (author)
  • Wingren, C. (author)
  • Lindmark, H. (author)
  • Wellner, A. (author)
  • Lundin, S. (author)
  • Yrlid, L. (author)
  • Ax, ElisabethGothenburg University,Göteborgs universitet,Krefting Research Centre (author)
  • Djukanovic, R. (author)
  • Sridhar, S. (author)
  • Higham, A. (author)
  • Singh, D. (author)
  • Southworth, T. (author)
  • Brightling, C. E. (author)
  • Olsson, H. K. (author)
  • Jevnikar, Z. (author)
  • Göteborgs universitetKrefting Research Centre (creator_code:org_t)

Related titles

  • In:European Respiratory Journal: European Respiratory Society (ERS)58:40903-19361399-3003

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