Post-translational modifications in the insoluble fraction of platelet-poor plasma distinguish pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS: a preliminary study
Rattachement africain : Afrique du Sud, ca, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Pre-COVID-19 Postural Orthostatic Tachycardia Syndrome (PC-POTS), Long COVID with initial orthostatic hypotension (LC-IOH), and Long COVID-POTS (LC-POTS) are primarily chronic post-viral conditions with debilitating symptoms, despite routine laboratory findings often being normal. We previously identified amyloidogenic fibrinaloid microclot complexes (FMCs) in the insoluble fraction of platelet-poor plasma (PPP-IF) in Long COVID, but it remains unclear whether similar abnormalities occur in PC-POTS and LC-POTS, or whether post-translational modifications (PTMs) contribute to disease mechanisms. Platelet-poor plasma from healthy controls ( n = 18), PC-POTS ( n = 20), LC-IOH ( n = 19), and LC-POTS ( n = 18) participants underwent proteomic analysis of the PPP-IF using double trypsin digestion and data-independent LC-MS/MS. Differential protein abundance, PTMs, and amyloidogenicity were compared across groups. Although few proteins were significantly dysregulated, extensive disease-specific PTM alterations were identified across coagulation, immune, and metabolic pathways. LC-IOH demonstrated prominent AGE- and oxidation-related PTMs on fibrinogen subunits, particularly fibrinogen alpha chain (FIBA), resembling diabetic glycation profiles. PC-POTS showed fewer fibrinogen PTMs but marked metabolic and immune dysregulation, including oxidised apoA1 and apoB and complement-associated proteins (C3, C4A/B, IC1), IGG1, and A2MG. LC-POTS shared coagulation-related features with LC-IOH and immune-related features with PC-POTS. Many dysregulated peptides were highly amyloidogenic in silico, consistent with β-sheet-rich FMCs. PTM dysregulation was substantially greater than protein-level changes. This study provides the first evidence that PTMs within the PPP-IF has the potential to distinctly differentiate PC-POTS, LC-IOH, and LC-POTS. Because PC-POTS samples predated SARS-CoV-2, their PTM signatures reflect intrinsic disease biology independent of COVID-19. PTM profiling revealed pro-coagulant fibrinogen changes in LC-IOH and LC-POTS, metabolic-oxidative dysregulation in LC-IOH and PC-POTS, and immune dysregulation in PC-POTS and LC-POTS. These abnormalities were not detectable by routine assays and may contribute to microvascular dysfunction. The findings support disease-specific biomarker development and targeted therapeutic strategies across autonomic and post-viral disorders.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Post-translational modifications in the insoluble fraction of platelet-poor plasma distinguish pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS: a preliminary study
- Date Crossref
- 23/07/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Stellenbosch University Department of Physiological Sciences Stellenbosch University, Afrique du Sud (code pays fourni par la source)Université ou école supérieure
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City of Cape Town City of Cape Town, Afrique du Sud (code pays fourni par la source)Organisme public
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Research ICT Africa Afrique du Sud (code pays fourni par la source)Organisation à but non lucratif
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Libin Cardiovascular Institute of Alberta pays non établi dans la noticeStructure de recherche
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University of Liverpool Department of Biochemistry pays non établi dans la noticeUniversité ou école supérieure
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Trace Labs Cape Town, Afrique du Sud (pays nommé en fin d’affiliation)Institution
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University of Calgary Libin Cardiovascular Institute pays non établi dans la noticeUniversité ou école supérieure
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Pulmonologist and sleep physician (medically retired) pays non établi dans la noticeInstitution
Department of Physiological Sciences — Stellenbosch University (Stellenbosch University, Afrique du Sud), City of Cape Town (City of Cape Town, Afrique du Sud) et Research ICT Africa (Afrique du Sud), avec 5 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.