Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome

Hoheisel, Friederike; Fleischer, Kathrin Maria; Rubarth, Kerstin; Sepúlveda, Nuno; Bauer, Sandra; Konietschke, Frank; Kedor Peters, Claudia; Stein, Annika Elisa; Wittke, Kirsten; Seifert, Martina; Bellmann-Strobl, Judith; Mautner, Josef; Behrends, Uta; Scheibenbogen, Carmen; Sotzny, Franziska

Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome

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Item Type:	Article
Title:	Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome
Creators Name:	Hoheisel, Friederike, Fleischer, Kathrin Maria, Rubarth, Kerstin, Sepúlveda, Nuno, Bauer, Sandra, Konietschke, Frank, Kedor Peters, Claudia, Stein, Annika Elisa, Wittke, Kirsten, Seifert, Martina, Bellmann-Strobl, Judith, Mautner, Josef, Behrends, Uta, Scheibenbogen, Carmen and Sotzny, Franziska
Abstract:	INTRODUCTION: Epstein-Barr virus (EBV) infection is a well-established trigger and risk factor for both myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID syndrome (PCS). In previous studies, we identified elevated IgG responses to arginine-rich (poly-R) sequences within the EBV nuclear antigens EBNA4 and EBNA6 in post-infectious ME/CFS (piME/CFS). Building on these findings, this exploratory study examines IgG reactivity to poly-R-containing EBV-derived peptides and homologous human peptides in women with PCS and ME/CFS. METHODS: IgG reactivity to poly-R containing peptides derived from EBNA4 and EBNA6, and homologous human 15-mer peptides and the corresponding full-length proteins, was assessed using a cytometric bead array (CBA) and a multiplex dot-blot assay. Serum samples were analyzed from 45 female PCS patients diagnosed according to WHO criteria, including 26 who also met the Canadian Consensus criteria for ME/CFS (pcME/CFS), 36 female patients with non-COVID post-infectious ME/CFS (piME/CFS), and 34 female healthy controls (HC). RESULTS: Autoantibodies targeting poly-R peptide sequences of the neuronal antigen SRRM3, the ion channel SLC24A3, TGF-β signaling regulator TSPLY2, and the angiogenesis-related protein TSPYL5, as well as full-length α-adrenergic receptor (ADRA) proteins, were more frequently detected in patient groups. Several of these autoantibodies showed positive correlations with core symptoms, including autonomic dysfunction, fatigue, cognitive impairment, and pain. CONCLUSION: This exploratory study identify autoantibodies directed against EBV mimicking arginine-rich sequences in human proteins, suggesting a potential role for molecular mimicry in the pathogenesis of PCS and ME/CFS.
Keywords:	Autoantibodies, Cross-Reactivity, EBV, Arginine-Rich Peptides, Post-COVID Syndrome, ME/CFS
Source:	Frontiers in Immunology
ISSN:	1664-3224
Publisher:	Frontiers Media SA
Volume:	16
Page Range:	1650948
Date:	19 September 2025
Official Publication:	https://doi.org/10.3389/fimmu.2025.1650948
PubMed:	View item in PubMed

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