TY - JOUR
T1 - Surface proteome of plasma extracellular vesicles as biomarkers for pneumonia and acute exacerbation of chronic obstructive pulmonary disease
AU - Jung, Anna Lena
AU - Møller Jørgensen, Malene
AU - Bæk, Rikke
AU - Griss, Kathrin
AU - Han, Maria
AU - Auf Dem Brinke, Kristina
AU - Timmesfeld, Nina
AU - Bertrams, Wilhelm
AU - Greulich, Timm
AU - Koczulla, Rembert
AU - Hippenstiel, Stefan
AU - Suttorp, Norbert
AU - Schmeck, Bernd
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - COPD
KW - EV Array
KW - acute exacerbation
KW - biomarker
KW - exosomes
KW - extracellular vesicles
KW - plasma
KW - pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85077346287&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiz460
DO - 10.1093/infdis/jiz460
M3 - Journal article
C2 - 31617573
SN - 0022-1899
VL - 221
SP - 325
EP - 335
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
IS - 2
ER -