Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery
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 bioma...
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BMC
2024-07-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-024-02315-x |
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| author | Massimo Nunes Mare Vlok Amy Proal Douglas B. Kell Etheresia Pretorius |
| author_facet | Massimo Nunes Mare Vlok Amy Proal Douglas B. Kell Etheresia Pretorius |
| author_sort | Massimo Nunes |
| collection | DOAJ |
| description | 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 |
| format | Article |
| id | doaj-art-c26ec39aa27443d79bc13b36befb76af |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-c26ec39aa27443d79bc13b36befb76af2025-02-09T12:10:47ZengBMCCardiovascular Diabetology1475-28402024-07-0123111410.1186/s12933-024-02315-xData-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machineryMassimo Nunes0Mare Vlok1Amy Proal2Douglas B. Kell3Etheresia Pretorius4Department of Physiological Sciences, Faculty of Science, Stellenbosch UniversityCentral Analytical Facility: Mass Spectrometry, Stellenbosch UniversityPolyBio Research FoundationDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityDepartment of Physiological Sciences, Faculty of Science, Stellenbosch UniversityAbstract 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 abstracthttps://doi.org/10.1186/s12933-024-02315-xMyalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS)ProteomicsThrombotic pathologyEndothelial pathology |
| spellingShingle | Massimo Nunes Mare Vlok Amy Proal Douglas B. Kell Etheresia Pretorius Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery Cardiovascular Diabetology Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) Proteomics Thrombotic pathology Endothelial pathology |
| title | Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery |
| title_full | Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery |
| title_fullStr | Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery |
| title_full_unstemmed | Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery |
| title_short | Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery |
| title_sort | data independent lc ms ms analysis of me cfs plasma reveals a dysregulated coagulation system endothelial dysfunction downregulation of complement machinery |
| topic | Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) Proteomics Thrombotic pathology Endothelial pathology |
| url | https://doi.org/10.1186/s12933-024-02315-x |
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