Extrazelluläre Vesikel als neue Biomarker bei der Diagnostik entzündlicher Lungenerkrankungen

Die ambulant erworbene Pneumonie (CAP) und die akut exazerbierte COPD (AECOPD) sind zwei häufige Erkrankungen, die weltweit mit einer hohen Morbidität und Mortalität einhergehen. Da sie sich klinisch sehr ähnlich präsentieren können, ist die Differentialdiagnostik schwierig. Kleine Extrazelluläre...

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Bibliographic Details
Main Author: Brinke, Kristina auf dem
Contributors: Schmeck, Bernd (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2021
Online Access:PDF Full Text
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Community-acquired pneumonia (CAP) and acute exacerbated COPD (AECOPD) are two common diseases associated with high morbidity and mortality worldwide. Due to similarities in their clinical presentation, differential diagnosis is difficult. Small extracellular vesicles (sEVs) are considered as potential as new biomarkers. Their surface proteins and other constituents are depending on their cell of origin and could be a step toward the anticipated "liquid biopsies". In this pilot study, we examined the surface proteins of plasma exosomes that possibly allow the differential diagnosis of CAP and AECOPD. For this purpose, 40 surface proteins were analysed by EV-array. The study was focused on the potential of the biomarkers to differentiate between the different study groups. Also, the ability of the parameters to estimate the severity of pneumonia was studied. Other parameters collected were blood count and CRP, clinical parameters and clinical scores (CRB-56, CURB, PSI, GOLD 1-4, GOLD A, B, C, D, and mMRC). In total, plasma samples from 55 human subjects were examined, including 24 CAP patients, 10 AECOPD patients and 21 healthy subjects. The EV array revealed significant differences between healthy subjects, CAP patients, and AECOPD patients. We found CD45 and CD28 to be the best discrimination markers on plasma exosomes between CAP and AECOPD with an AUC > 0.92 in a ROC analysis. To distinguish between CAP patients and healthy subjects, CD45 and CD16 showed the best results. A classification into uncomplicated and severe CAP was possible with ICAM-1. Since the diagnosis of CAP in COPD patients is particularly difficult, it was investigated whether a distinction between CAP and AECOPD is possible even if the CAP patient had COPD. Here, the ensemble feature selection resulted in a panel consisting of CD45, CD28, CTLA4, TNF-R-II and CD16. All in all, the EV array is a simple and minimal-invasive diagnostic tool with potential to distinguish between healthy subjects, CAP patients, and AECOPD patients. Further studies with bigger cohorts are needed to explore the potential of sEV proteins as new biomarkers in the diagnosis of infectious lung diseases.