PuSH - Publikationsserver des Helmholtz Zentrums München: 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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Hoheisel, F.* ; Fleischer, K.M. ; Rubarth, K.* ; Sepúlveda, N.* ; Bauer, S.* ; Konietschke, F.* ; Kedor Peters, C.* ; Stein, A.E.* ; Wittke, K.* ; Seifert, M.* ; Bellmann-Strobl, J.* ; Mautner, J. ; Behrends, U.* ; Scheibenbogen, C.* ; Sotzny, F.*

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

Front. Immunol. 16:1650948 (2025)

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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.

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