PMID- 31170500 OWN - NLM STAT- MEDLINE DCOM- 20200812 LR - 20200812 IS - 1876-7737 (Electronic) IS - 1874-3919 (Linking) VI - 204 DP - 2019 Jul 30 TI - Proteomics characterization of extracellular vesicles sorted by flow cytometry reveals a disease-specific molecular cross-talk from cerebrospinal fluid and tears in multiple sclerosis. PG - 103403 LID - S1874-3919(19)30175-7 [pii] LID - 10.1016/j.jprot.2019.103403 [doi] AB - Several proteomics studies have been conducted to identify new cerebrospinal fluid (CSF) biomarkers in Multiple Sclerosis (MuS). However, the complexity of CSF and its invasive collection, limits its use. Therefore, the goal of biomarker research in MuS is to identify novel distinctive targets in CSF or in easily accessible biofluids. Tears represent an interesting matrix for this purpose, because (1) tears are related to the central nervous system (CNS) and (2) the CNS contains Extracellular Vesicles (EVs) derived from brain cells. These EVs are emerging new biomarkers associated to several neurological disorders. Here we applied an optimized flow cytometer for the identification and subtyping of EVs from CSF and tears. We found, for the first time, microglia-derived and neural-derived EVs in tears. The flow cytometer was used to sort and purify 10(6) EVs from untouched CSF and tears of MuS patients and healthy subjects. Purified EVs were analyzed with shotgun proteomics analysis, revealing that EVs from both CSF and tears of MuS patients conveyed similar proteins. Our data demonstrated a specific EVs-mediated molecular cross talk between CSF and tears, which opens the door to new diagnostic perspectives for MuS. Data are available via ProteomeXchange with identifier PXD013794. SIGNIFICANCE: Proteomics characterization of released Extracellular Vesicles (EVs) in CSF and tears of Multiple Sclerosis patients represents a pioneering application that helped in recognizing information about the biologically relevant molecules. We found, for the first time, microglia-derived and neural-derived EVs in tears. Moreover, purified EVs revealed that both CSF and tears of Multiple Sclerosis patients conveyed similar proteins involved in inflammation, angiogenesis and immune response signalling. We think that our data will contribute to enhance knowledge in Multiple Sclerosis mechanisms and help in biomarker discovery. Moreover tears represent one of the most convenient body fluid for biomarker discovery in Multiple Sclerosis, since it is an high informative and easy accessible. The opportunity to export such a platform to a territory monitoring plan opens the door to new diagnostic perspectives for Multiple Sclerosis. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Pieragostino, Damiana AU - Pieragostino D AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Lanuti, Paola AU - Lanuti P AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Cicalini, Ilaria AU - Cicalini I AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Cufaro, Maria Concetta AU - Cufaro MC AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Ciccocioppo, Fausta AU - Ciccocioppo F AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Ronci, Maurizio AU - Ronci M AD - Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Simeone, Pasquale AU - Simeone P AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Onofrj, Marco AU - Onofrj M AD - Unit of Neurology Ss Annunziata Hospital, Chieti, Italy; Department of Neuroscience, Imaging and Clinical Sciences University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - van der Pol, Edwin AU - van der Pol E AD - Biomedical Engineering and Physics, Laboratory Experimental Clinical, Vesicle Observation Center, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef, Amsterdam, the Netherlands. FAU - Fontana, Antonella AU - Fontana A AD - Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Marchisio, Marco AU - Marchisio M AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. FAU - Del Boccio, Piero AU - Del Boccio P AD - Centre on Aging Sciences and Translational Medicine (Ce.SI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. Electronic address: piero.delboccio@unich.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190603 PL - Netherlands TA - J Proteomics JT - Journal of proteomics JID - 101475056 RN - 0 (Biomarkers) SB - IM MH - Biomarkers/cerebrospinal fluid MH - Cerebrospinal Fluid/*metabolism MH - Extracellular Vesicles/*metabolism MH - *Flow Cytometry MH - Humans MH - Multiple Sclerosis/*cerebrospinal fluid MH - Tears/*metabolism OTO - NOTNLM OT - CSF OT - Extracellular vesicles OT - FACS sorting OT - Multiple sclerosis OT - Proteomics OT - Tears EDAT- 2019/06/07 06:00 MHDA- 2020/08/13 06:00 CRDT- 2019/06/07 06:00 PHST- 2019/03/25 00:00 [received] PHST- 2019/05/14 00:00 [revised] PHST- 2019/05/31 00:00 [accepted] PHST- 2019/06/07 06:00 [pubmed] PHST- 2020/08/13 06:00 [medline] PHST- 2019/06/07 06:00 [entrez] AID - S1874-3919(19)30175-7 [pii] AID - 10.1016/j.jprot.2019.103403 [doi] PST - ppublish SO - J Proteomics. 2019 Jul 30;204:103403. doi: 10.1016/j.jprot.2019.103403. Epub 2019 Jun 3.