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- Medina, LMP, et al.
(författare)
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Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
- 2023
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 24:1, s. 62-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
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- Lozano, IMD, et al.
(författare)
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Proteome profiling of whole plasma and plasma-derived extracellular vesicles facilitates the detection of tissue biomarkers in the non-obese diabetic mouse
- 2022
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 971313-
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which pancreatic beta cells are destroyed in type 1 diabetes (T1D) remains to be fully understood. Recent observations indicate that the disease may arise because of different pathobiological mechanisms (endotypes). The discovery of one or several protein biomarkers measurable in readily available liquid biopsies (e.g. blood plasma) during the pre-diabetic period may enable personalized disease interventions. Recent studies have shown that extracellular vesicles (EVs) are a source of tissue proteins in liquid biopsies. Using plasma samples collected from pre-diabetic non-obese diabetic (NOD) mice (an experimental model of T1D) we addressed if combined analysis of whole plasma samples and plasma-derived EV fractions increases the number of unique proteins identified by mass spectrometry (MS) compared to the analysis of whole plasma samples alone. LC-MS/MS analysis of plasma samples depleted of abundant proteins and subjected to peptide fractionation identified more than 2300 proteins, while the analysis of EV-enriched plasma samples identified more than 600 proteins. Of the proteins detected in EV-enriched samples, more than a third were not identified in whole plasma samples and many were classified as either tissue-enriched or of tissue-specific origin. In conclusion, parallel profiling of EV-enriched plasma fractions and whole plasma samples increases the overall proteome depth and facilitates the discovery of tissue-enriched proteins in plasma. If applied to plasma samples collected longitudinally from the NOD mouse or from models with other pathobiological mechanisms, the integrated proteome profiling scheme described herein may be useful for the discovery of new and potentially endotype specific biomarkers in T1D.
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