{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:26:49Z","timestamp":1789165609883,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charit\u00e9 Chronic Fatigue Center (CFC) of the Charit\u00e9 Universit\u00e4tsmedizin Berlin"},{"name":"German Society for ME\/CFS"},{"DOI":"10.13039\/501100002347","name":"BMFTR-funded projects BioSig-PEM","doi-asserted-by":"publisher","award":["01EJ2408D"],"award-info":[{"award-number":["01EJ2408D"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"VADYS-ME","doi-asserted-by":"publisher","award":["01EJ2406A"],"award-info":[{"award-number":["01EJ2406A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lost Voices Foundation e.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-infectious Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) is a chronic disease with unresolved pathophysiology and limited diagnostic options. Extracellular vesicles (EVs) carry disease-specific protein and miRNA signatures and may enable improved disease profiling. We aimed to identify novel protein and miRNA markers as potential biomarkers in plasma EVs from female ME\/CFS patients, including post-COVID-19 ME\/CFS and post-infectious ME\/CFS of other origins, compared with healthy controls. EVs were isolated from plasma by size-exclusion chromatography and characterized for number, size, morphology, and surface marker expression. Flow cytometry showed that small EVs strongly expressed tetraspanins, with only minor differences between ME\/CFS patients and healthy donors. Proteomic profiling of EVs from ME\/CFS patients identified altered cargo proteins, including hemoglobin subunit alpha and insulin-like growth factor-binding protein acid labile subunit compared with healthy controls (n \u2264 10\/cohort). Small RNA sequencing followed by qPCR revealed significant downregulation of hsa-let-7b-5p in EVs from post-COVID-19 ME\/CFS patients (n = 12) versus healthy controls (n = 15). Reduced hsa-let-7b-5p expression correlated with impaired physical functioning and increased fatigue, pain, and immune activation. These findings indicate that EV cargo differences, particularly hemoglobin subunit alpha and insulin-like growth factor-binding protein acid labile subunit, as well as hsa-let-7b-5p, represent promising candidates for ME\/CFS diagnosis and patient stratification.<\/jats:p>","DOI":"10.3390\/ijms27052314","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:39:56Z","timestamp":1772455196000},"page":"2314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME\/CFS Patients"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-9769","authenticated-orcid":false,"given":"Martina","family":"Seifert","sequence":"first","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"BIH-Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Sch\u00e4fers","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona F.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Schwarzburg","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Boristowski","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4080-8809","authenticated-orcid":false,"given":"Anne","family":"Birke","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Klein","sequence":"additional","affiliation":[{"name":"BIH-Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1593-8563","authenticated-orcid":false,"given":"Franziska","family":"Sotzny","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-6346","authenticated-orcid":false,"given":"Kerstin","family":"Rubarth","sequence":"additional","affiliation":[{"name":"Institute of Biometry and Clinical Epidemiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2916-0852","authenticated-orcid":false,"given":"Lara","family":"Windzio","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2800-4949","authenticated-orcid":false,"given":"Christien M.","family":"Beez","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charit\u00e9 (DHZC), 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-9213","authenticated-orcid":false,"given":"Claudia Kedor","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Wittke","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-9638","authenticated-orcid":false,"given":"Carmen","family":"Scheibenbogen","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-182X","authenticated-orcid":false,"given":"Anna","family":"Greco","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2796.2011.02428.x","article-title":"Myalgic encephalomyelitis: International Consensus Criteria","volume":"270","author":"Carruthers","year":"2011","journal-title":"J. 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