Surface proteome of plasma extracellular vesicles as biomarkers for pneumonia and acute exacerbation of chronic obstructive pulmonary disease

Anna Lena Jung, Malene Møller Jørgensen, Rikke Bæk, Kathrin Griss, Maria Han, Kristina Auf Dem Brinke, Nina Timmesfeld, Wilhelm Bertrams, Timm Greulich, Rembert Koczulla, Stefan Hippenstiel, Norbert Suttorp, Bernd Schmeck

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs).

METHODS: We performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies.

RESULTS: We detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor-R-II, and CD16.

CONCLUSION: The discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Volume221
Issue number2
Pages (from-to)325-335
Number of pages11
ISSN0022-1899
DOIs
Publication statusPublished - Jan 2020

Keywords

  • COPD
  • EV Array
  • acute exacerbation
  • biomarker
  • exosomes
  • extracellular vesicles
  • plasma
  • pneumonia

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