[...] LC-MS/MS analysis of ME/CFS plasma reveals dysregulated coagulation [...], endothelial dysfunction, [...], 2024, Nunes, Kell, Pretorius et al

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Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery

Massimo Nunes, Mare Vlok, Amy Proal, Douglas B. Kell, Etheresia Pretorius

Published 16 July 2024

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes.

To build on these findings, and to identify potential biomarkers that can be related to pathophysiology, we measured differences in protein expression in platelet-poor plasma (PPP) samples from 15 ME/CFS study participants and 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS.

We identified 24 proteins that are significantly increased in the ME/CFS group compared to the controls, and 21 proteins that are significantly downregulated. Proteins related to clotting processes – thrombospondin-1 (important in platelet activation), platelet factor 4, and protein S – were differentially expressed in the ME/CFS group, suggestive of a dysregulated coagulation system and abnormal endothelial function. Complement machinery was also significantly downregulated, including C9 which forms part of the membrane attack complex. Additionally, we identified a significant upregulation of lactotransferrin, protein S100-A9, and an immunoglobulin variant.

The findings from this experiment further implicate the coagulation and immune system in ME/CFS, and bring to attention the pathology of or imposed on the endothelium. This study highlights potential systems and proteins that require further research with regards to their contribution to the pathogenesis of ME/CFS, symptom manifestation, and biomarker potential, and also gives insight into the hematological and cardiovascular risk for ME/CFS individuals affected by diabetes mellitus.

Graphical abstract
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Link (Cardiovascular Diabetology) [Open access]
 
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That's been their go-to journal. Prior to this includes —

Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study (2013, Cardiovascular Diabetology)

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics (2015, Cardiovascular Diabetology)

Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains (2017, Cardiovascular Diabetology)

Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation (2019, Cardiovascular Diabetology)

Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma: a preliminary report (2020, Cardiovascular Diabetology)

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 PASC is accompanied by increased levels of antiplasmin (2021, Cardiovascular Diabetology)

Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 PASC shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system (2022, Cardiovascular Diabetology)

Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 PASC (2022, Cardiovascular Diabetology)
 
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Pretorius on editorial board… that’s why they are submitting there… doesn’t inspire confidence actually.

Editorial Board
Victor Aboyans, MD, PhD, FAHA, FESC, Department of Cardiology, Dupuytren Hospital and Limoges University, Limoges, France
Professor Yehuda Adler, MD, MPH, Faculty of Medicine, Tel Aviv University, Israel
Professor Eddy Barasch, MD, St. Francis Hospital, Hartford, CT, USA
Antonio Ceriello, MD, PhD, IRCCS MultiMedica, Milan, Italy
Amanda J Cox, PhD, Griffith University, Southport, Australia
Sergio Dubner, MD, Clínica y Maternidad Suizo Argentina, Buenos Aires, Argentina
Professor Abdalla El-Mowafy, PhD, Mansoura University, Mansoura, Egypt
Professor Ricardo J. Esper, MD, FACC, Buenos Aires University, Buenos Aires, Argentina
Professor Gian Paolo Fadini, MD, PhD, University of Padova, Padua, Italy
Professor Almudena Gómez-Hernández, PhD, Universidad Complutense de Madrid, Madrid, Spain
Byron J. Hoogwerf, MD, FACP, FACE, Cleveland Clinic and Eli Lilly & Co. (retired) FL, USA
Professor Rodrigo Jiménez-García, MD, PhD, MPH, Complutense University of Madrid, Spain
Naoto Katakami, MD, PhD, Osaka University Graduate School of Medicine, Japan
Professor Robert Klempfner, MD, Tel Aviv University, Faculty of Medicine, Israel
Gary D Lopaschuk, PhD, University of Alberta, Edmonton, Canada
Professor Norikazu Maeda, MD, PhD, Department of Endocrinology, Metabolism and Diabetes, Faculty of Medicine, Kindai University, Japan
Paolo Marzullo, MD, PhD, Università Piemonte Orientale, Novara, Italy
Jordi Merino, PhD, Massachusetts General Hospital, Boston, MA, USA
Professor Michael Motro, MD, FACC, FAHA, Faculty of Medicine, Tel Aviv University, Israel
James T. Pearson, PhD, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
Etheresia Pretorius, PhD, Stellenbosch University, Stellenbosch, South Africa
Giuseppe Pugliese, MD, PhD, La Sapienza University, Rome, Italy
Professor Giuseppe M. Rosano, MD, PhD, M.Sc., St George's Hospitals NHS Trust University of London, London, UK
Gil S Salles, MD, PhD, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Eberhard Standl, MD, PhD, Munich Diabetes Research Group, Munich, Germany
Professor Ki-chul Sung, MD, Kangbuk Samsung Hospital, Seoul, South Korea
Professor Gilad Twig, MD, MPH, PhD,Institute of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Israel
Charissa E van den Brom, PhD, VU University Medical Center, Amsterdam, Netherlands
Professor Suowen Xu, PhD, University of Science and Technology of China, Hefei, China
Yung-Hsin Yeh, MD, Chung-Gung University and Chang-Gung Memorial Hospital, Taoyuan, Taiwan
Jian Zhou, PhD, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
 
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