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@ARTICLE{Wetzel:282954,
      author       = {Wetzel, Nora Sandrine and Kulsvehagen, Laila and Lecourt,
                      Anne-Catherine and Filipek, Beata and Lipps, Patrick and
                      Rieder, Laura and Berve, Kristina and Krishnamoorthy,
                      Gurumoorthy and 't Hart, Bert A and Schirmer, Lucas and
                      Yandamuri, Soumya S and O'Connor, Kevin C and Pröbstel,
                      Anne-Katrin},
      title        = {{P}atient-{D}erived {M}onoclonal {M}yelin {O}ligodendrocyte
                      {G}lycoprotein {A}utoantibodies {M}ediate {C}ytotoxicity.},
      journal      = {Neurology: Neuroimmunology $\&$ Neuroinflammation ;
                      official journal of the American Academy of Neurology},
      volume       = {13},
      number       = {1},
      issn         = {2332-7812},
      address      = {Philadelphia, Pa.},
      publisher    = {Wolters Kluwer},
      reportid     = {DZNE-2025-01415},
      pages        = {e200520},
      year         = {2026},
      abstract     = {Serum myelin oligodendrocyte glycoprotein (MOG) antibodies
                      are a hallmark of the newly defined neuroinflammatory
                      disease entity MOG antibody-associated disease (MOGAD). Yet,
                      the lack of patient-derived recombinant human MOG
                      (hMOG)-reactive autoantibodies limits investigations into
                      the molecular mechanisms by which these autoantibodies
                      mediate CNS pathology, thereby hindering rational
                      therapeutic approaches. To understand the origins and
                      disease-relevant mechanisms of autoantibodies in MOGAD, we
                      generated and characterized monoclonal anti-hMOG antibodies
                      (MOG-mAbs) from circulating B cells of patients with
                      MOGAD.We isolated MOG-specific B-cell receptor (BCR)
                      sequences from unique circulating B-cell clones of 6
                      patients with MOGAD using an antigen selection approach. BCR
                      sequences were expressed as immunoglobulin (Ig)G1
                      antibodies, and their molecular features, epitope
                      specificity, and binding to MOG isoforms were investigated.
                      The MOG-mAbs' ability to mediate antibody-dependent cellular
                      phagocytosis (ADCP), natural killer (NK) cell-mediated
                      antibody-dependent cellular cytotoxicity (ADCC), and
                      complement-dependent cytotoxicity (CDC) toward
                      MOG-expressing cells was assessed by live cell-based
                      assays.Of the 15 MOG-mAbs generated, 4 revealed evidence of
                      affinity maturation, whereas the remaining 11 were germline
                      encoded. Binding capacities to hMOG varied considerably,
                      with the most frequent putative epitope mapping to a region
                      that includes residue P42. The efficacy of these antibodies
                      in mediating ADCP, ADCC, and CDC of MOG-expressing cells was
                      heterogeneous and associated with their binding
                      characteristics to MOG and its isoforms.Taken together, the
                      molecular characteristics and binding patterns of these
                      patient-derived MOG-mAbs reveal a diverse repertoire of
                      MOG-binding autoantibodies with pathogenic capacity in
                      vitro. Consequently, these well-characterized patient
                      autoantibodies offer a foundation for developing in vivo
                      models of MOGAD, serve as tools to standardize diagnostic
                      assays, and guide development of therapeutic strategies
                      targeting either B cells or autoantibodies and their
                      effector functions.},
      keywords     = {Humans / Myelin-Oligodendrocyte Glycoprotein: immunology /
                      Autoantibodies: immunology / Antibodies, Monoclonal:
                      immunology / Female / Male / Adult / Middle Aged /
                      B-Lymphocytes: immunology / Antibody-Dependent Cell
                      Cytotoxicity: immunology / Myelin-Oligodendrocyte
                      Glycoprotein (NLM Chemicals) / Autoantibodies (NLM
                      Chemicals) / MOG protein, human (NLM Chemicals) /
                      Antibodies, Monoclonal (NLM Chemicals)},
      cin          = {AG Pröbstel},
      ddc          = {610},
      cid          = {I:(DE-2719)1013045},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41406408},
      doi          = {10.1212/NXI.0000000000200520},
      url          = {https://pub.dzne.de/record/282954},
}