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@ARTICLE{Vogelgesang:281503,
      author       = {Vogelgesang, Antje and Steinmetz, Anke and Stufano, Angela
                      and Schino, Valentina and Plantone, Domenico and Flöel,
                      Agnes and Lucchese, Guglielmo},
      title        = {{A}nti-neuronal and anti-mitochondrial autoantibodies are
                      associated with lower functional status and more severe
                      respiratory symptoms in post {COVID} syndrome.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DZNE-2025-01124},
      pages        = {1642250},
      year         = {2025},
      abstract     = {We previously identified IgG autoantibodies targeting
                      epitopes within brainstem proteins-disabled homolog 1
                      (DAB1), apoptosis-inducing factor 1 (AIFM1), and surfeit
                      locus protein 1 (SURF1)-as markers of severe acute COVID-19.
                      This study investigates whether the same autoantibodies
                      contribute to the pathophysiology of Post COVID Syndrome
                      (PCS).Using a multiplexed bead-based immunoassay, we
                      measured IgG levels against 18 synthetic peptides derived
                      from DAB1, AIFM1, and SURF1 in serum samples from 45 PCS
                      patients and 30 post-COVID controls without long-term
                      symptoms. We employed generalized linear mixed models (GLMM)
                      and nonlinear principal component analysis (CATPCA) to
                      explore associations between antibody levels and clinical
                      variables, including functional status (PCFS), respiratory
                      symptoms, fatigue, cognitive impairment (as assessed by the
                      Montreal Cognitive Assessment, MoCA), and mood.Higher IgG
                      levels against the three autoantigens significantly
                      predicted PCS at 3 months postinfection (t=2.21, p=0.03),
                      whereas antibodies against a control peptide (polio) showed
                      no such association. CATPCA identified a principal component
                      capturing respiratory symptoms and functional impairment
                      (PCFS), which was also significantly predicted by
                      autoantibody levels (t=2.04, p=0.04). MoCA scores did not
                      correlate with autoantibody levels, and subjective cognitive
                      complaints were paradoxically linked to lower antibody
                      titers and fewer physical symptoms.The findings from the
                      present explorative study, although largely correlative,
                      appear to suggest a sustained autoimmune response targeting
                      neuronal and mitochondrial proteins in PCS, particularly
                      associated with respiratory dysfunction and reduced
                      functional capacity. The results also highlight potential
                      limitations of standard cognitive screening tools like the
                      MoCA in detecting subtle deficits in PCS. The identified
                      autoantibodies may serve as biomarkers for persistent
                      post-COVID disability. Future research replicating present
                      results on larger samples and specifically investigating a
                      causal link between occurrence of the Auto-Abs and PCS is
                      needed for shaping future immunomodulatory therapeutic
                      strategies.},
      keywords     = {Humans / Autoantibodies: blood / Autoantibodies: immunology
                      / Female / Male / Middle Aged / COVID-19: immunology /
                      COVID-19: complications / SARS-CoV-2: immunology / Aged /
                      Immunoglobulin G: blood / Immunoglobulin G: immunology /
                      Adult / Mitochondria: immunology / Mitochondrial Proteins:
                      immunology / Autoantigens: immunology / Neurons: immunology
                      / Biomarkers: blood / Post-Acute COVID-19 Syndrome /
                      Membrane Proteins: immunology / Nerve Tissue Proteins:
                      immunology / Adaptor Proteins, Signal Transducing:
                      immunology / autoantibodies (Other) / autoimmunity (Other) /
                      brainstem (Other) / mitochondria (Other) / post COVID
                      (Other) / Autoantibodies (NLM Chemicals) / Immunoglobulin G
                      (NLM Chemicals) / Mitochondrial Proteins (NLM Chemicals) /
                      Autoantigens (NLM Chemicals) / Biomarkers (NLM Chemicals) /
                      Membrane Proteins (NLM Chemicals) / Nerve Tissue Proteins
                      (NLM Chemicals) / Adaptor Proteins, Signal Transducing (NLM
                      Chemicals)},
      cin          = {AG Flöel},
      ddc          = {610},
      cid          = {I:(DE-2719)5000081},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40995367},
      pmc          = {pmc:PMC12454094},
      doi          = {10.3389/fimmu.2025.1642250},
      url          = {https://pub.dzne.de/record/281503},
}