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Original research
Clinical, prognostic and pathophysiological implications of MOG-IgG detection in the CSF: the importance of intrathecal MOG-IgG synthesis
  1. Giacomo Greco1,2,
  2. Mario Risi3,
  3. Stefano Masciocchi1,4,
  4. Pietro Businaro1,4,
  5. Eleonora Rigoni2,
  6. Elisabetta Zardini1,4,
  7. Silvia Scaranzin4,
  8. Chiara Morandi4,
  9. Luca Diamanti5,
  10. Thomas Foiadelli6,
  11. Maria Pia Giannoccaro7,8,
  12. Luana Morelli8,
  13. Rocco Liguori7,8,
  14. Paolo Barone9,
  15. Alessandra Tozzo10,
  16. Alice Passarini11,
  17. Stefano Gelibter12,
  18. Francesco Patti13,14,
  19. Paola Banfi15,
  20. Anna Maria Simone16,
  21. Alvino Bisecco3,
  22. Martino Ruggieri17,
  23. Davide Maimone18,
  24. Giorgia Bruno3,19,
  25. Sabrina Siliquini20,
  26. Stefania Bova21,
  27. Massimiliano Di Filippo22,
  28. Roberta Lanzillo23,
  29. Antonio Gallo3,
  30. Elena Colombo2,
  31. Diego Franciotta4,
  32. Matteo Gastaldi4
  33. on behalf of the Neuroimmunology Platform (PNI) study group
    1. 1Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
    2. 2Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy
    3. 3Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Napoli, Italy
    4. 4Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy
    5. 5Neuroncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy
    6. 6Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
    7. 7Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
    8. 8IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
    9. 9Neurology Unit, University Hospital 'San Giovanni di Dio e Ruggi d’Aragona', Salerno, Italy
    10. 10Department of Pediatric Neuroscience, Foundation IRCCS Carlo Besta Neurological Institute, Milano, Italy
    11. 11Child Neuropsychiatry Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    12. 12Department of Neurosciences, Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
    13. 13University of Catania, Department of Surgical and Medical Sciences and Advanced Technologies 'G.F. Ingrassia', Catania, Italy
    14. 14UOS Sclerosi Multipla, Gaspare Rodolico Hospital, Catania, Italy
    15. 15Neurology and Stroke Unit, Ospedale di Circolo/Fondazione Macchi, ASST Sette Laghi, Varese, Italy
    16. 16Neurology Unit, Carpi Hospital, AUSL Modena, Carpi, Italy
    17. 17Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
    18. 18Centro Sclerosi Multipla, UOC Neurologia, Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy
    19. 19Pediatric Neurology Unit, Department of Neurosciences, Santobono Pausilipon Azienda Ospedaliera Pediatrica, Napoli, Italy
    20. 20Child Neurology and Psychiatry Unit, 'G. Salesi' Children’s Hospital, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
    21. 21Pediatric Neurology Unit, Buzzi Children's Hospital, Milano, Italy
    22. 22Section of Neurology, University of Perugia, Department of Medicine and Surgery, Perugia, Italy
    23. 23Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Naples Federico II, Napoli, Italy
    1. Correspondence to Dr Matteo Gastaldi, Neuroimmunology laboratory, IRCCS Mondino Foundation, Pavia, 27100, Italy; matteo.gastaldi{at}mondino.it

    Abstract

    Background Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS).

    Methods We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF− and ITS+/ITS− patients.

    Results MOG-IgG were found in 55/960 patients (5.7%; serum+/CSF−: 58.2%, serum+/CSF+: 34.5%; serum−/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI −0.46 to –0.65), p=0.65). There were no clinical–paraclinical differences between MOG-IgG CSF+ vs CSF− patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01).

    Conclusions Consistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

    • NEUROIMMUNOLOGY
    • IMMUNOLOGY
    • MULTIPLE SCLEROSIS

    Data availability statement

    Data are available in a public, open access repository. Anonymised data not published within this article will be made available by request from any qualified investigator. Raw data are available at the Zenodo repository (doi:10.5281/zenodo.10405063).

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    Data availability statement

    Data are available in a public, open access repository. Anonymised data not published within this article will be made available by request from any qualified investigator. Raw data are available at the Zenodo repository (doi:10.5281/zenodo.10405063).

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    Footnotes

    • Collaborators The PNI (Neuroimmunology Platform Group): Roberto Bergamaschi, Enrico Marchioni, Elisa Vegezzi, Paola Bini, Eleonora Tavazzi, Lara Ahmad, Fortuna Ricciardiello, Laura Giordano, Antonella Toriello, Cristian Sorrentino, Alice Passarini, Pierluigi Smilari, Monica Anna Maria Lodi, Antonio Lucia Spiezia.

    • Contributors GG and MG had full access to all of the data of the study and MG is responsible for the overall content as guarantor. GG, MG and DF contributed to the conception and design of the study, and to statistical analyses. All authors contributed to acquisition, analysis and interpretation of the data. Authors of the PNI Study Group have contributed to acquisition, analysis and interpretation of the data. GG, DF and MG contributed to drafting the text and preparing the figures. All authors contributed to the critical review of the manuscript for important intellectual content. MG obtained funding and supervised GG.

    • Funding This project was funded by the Ministero della Salute - Ricerca Corrente 2022-2024 (RRC2024-23684441) grant to the IRCCS Mondino Foundation

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer-reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.