Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome

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dc.contributor.authorAzcue, N.
dc.contributor.authorPrada, A.
dc.contributor.authorPino Sáez, Rocío del
dc.contributor.authorAcera Gil, María Ángeles
dc.contributor.authorFernández Valle, Tamara
dc.contributor.authorAyo Mentxakatorre, Naia
dc.contributor.authorPérez Concha, Tomás
dc.contributor.authorMurueta-Goyena Larrañaga, Ane
dc.contributor.authorLafuente, Jose Vicente
dc.contributor.authorLópez de Munain Arregui, Adolfo
dc.contributor.authorRuiz Irastorza, Guillermo
dc.contributor.authorRibacoba Bajo, Laureano
dc.contributor.authorGabilondo Cuellar, Iñigo
dc.contributor.authorTijero Merino, Beatriz
dc.contributor.authorGómez Esteban, Juan Carlos
dc.date.accessioned2026-08-11T07:39:26Z
dc.date.available2026-08-11T07:39:26Z
dc.date.issued2026
dc.date.updated2026-08-11T07:39:26Z
dc.description.abstractPost-COVID condition (PCC) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic disorders marked by fatigue, autonomic dysfunction, and cognitive impairment. Autoantibodies (AAbs) targeting adrenergic and muscarinic receptors have been implicated in their pathophysiology. This study aimed to investigate the association between these AAbs, autonomic nervous system (ANS) function, and cognitive performance in PCC and ME/CFS. We included 96 PCC patients, 59 ME/CFS patients, and 36 healthy controls (HCs). Plasma AAbs against α1, β1, β2 adrenergic and M1–M4 muscarinic receptors were measured via ELISA. ANS function was evaluated using COMPASS-31, Sudoscan, hemodynamic tests (deep breathing, Valsalva, tilt test), and heart rate variability. Cognitive domains assessed included attention, fluency, processing speed, memory, visuoconstruction, perception, and executive functions. ME/CFS patients had significantly higher β2 adrenergic AAb titers than PCC and HCs (F₂,₁₈₆ = 3.15, p = 0.046). PCC patients showed more borderline/pathological M3 muscarinic AAb results compared to HCs. β2 AAb levels correlated with increased autonomic symptoms in PCC (r = 0.27, p = 0.048) and sympathovagal imbalance in ME/CFS (r = 0.45, p = 0.001). In ME/CFS, M1, M3, and M4 AAb titers positively correlated with verbal and working memory performance. Distinct AAb profiles in PCC and ME/CFS suggest potential differences in immunological mechanisms. β2 adrenergic receptor AAbs were associated with measures of autonomic dysfunction in PCC patients, and with sympathovagal parameters in ME/CFS patients. Muscarinic AAbs were correlated with cognitive performance in ME/CFS, supporting a potential role of these autoantibodies in autonomic and cognitive dysfunction. These findings support further investigation of AAbs as biomarkers and therapeutic targets.en
dc.description.sponsorshipThis study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI20/01076 and co‑funded by the European Union, BIOEF through EITB maratoia (BIOS21/COV/006), and grants for health research projects from the Basque Government (2021111006, 2022111016, 2025333035). The first author received a pre‑doctoral research grant from the Basque government (PRE_2024_2_0237). RDP was supported by the Spanish Ministry of Science, Innovation and Universities and the State Research Agency (MCIN/AEI/10.13039/501100011033) through a Ramón y Cajal Fellowship (RYC2024-049664-I), and by Ikerbasque, the Basque Foundation for Science.en
dc.identifier.citationAzcue, Prada, Del Pino, Acera, Fernández-Valle, Ayo-Mentxakatorre, Pérez-Concha, Murueta-Goyena, Lafuente, López de Munain, Ruiz Irastorza, Ribacoba, Gabilondo, Tijero-Merino, & Gómez-Esteban. (2026). Involvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndrome. Scientific Reports, 16(1). https://doi.org/10.1038/S41598-026-49131-9
dc.identifier.doi10.1038/S41598-026-49131-9
dc.identifier.eissn2045-2322
dc.identifier.urihttps://hdl.handle.net/20.500.14454/6490
dc.language.isoeng
dc.publisherNature Research
dc.rights© The Author(s) 2026
dc.subject.otherAdrenergic receptor antibodies
dc.subject.otherDysautonomia
dc.subject.otherMuscarinic receptor antibodies
dc.subject.otherMyalgic Encephalomyelitis/Chronic Fatigue Syndrome
dc.subject.otherPost-COVID condition
dc.titleInvolvement of autoantibodies against G protein-coupled receptors in post-COVID condition and Chronic Fatigue Syndromeen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue1
oaire.citation.titleScientific Reports
oaire.citation.volume16
oaire.licenseConditionhttps://creativecommons.org/licenses/by-nc-nd/4.0/
oaire.versionVoR
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