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Cell-based assays for the detection of MOG antibodies: a comparative study

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Abstract

Background

The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection.

Methods

Consecutive sera from 204 patients with ‘possible MOGAD’ (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgGH+L), and a live-CBA for IgG1 (LCBA-IgG1). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgGFcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgGFcγ).

Results

Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8–95.9) and specificity 93.3% (CI:88.0–96.7) for LCBA-IgGH+L, and 74.6% (CI:61.0–85.3) and 100% (CI:97.6–100) for LCBA-IgG1. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG1); of these, three with ‘possible MOGAD’ showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG2, whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 ‘possible MOGAD’, 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1–98.4) and specificity 97.0% (CI:83.8–99.9) for LCBA-IgGFcγ, and 87.2% (CI:72.6–95.7) and 97.0% (CI:83.8–99.9) for FCBA-IgGFcγ.

Conclusions

LCBA-IgG1 showed the highest specificity but can miss MOG-IgG2 reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgGH+L/ IgGFcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgGFcγ yielded the highest accuracy, and FCBA-IgGFcγ good specificity, but it was at risk of false-negative results.

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Data availability

All data from the present study are available upon request to the corresponding author.

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Acknowledgements

We thank Mark Woodhall and Angela Vincent for the support in implementing the CBAs used for this study.

Funding

This work was supported by the Italian Ministry of Health ‘Ricerca Corrente’ 2017–2019 Grant (Grant code: RC1812C) to the IRCCS Mondino Foundation.

Author information

Authors and Affiliations

  1. Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy

    Matteo Gastaldi, Silvia Scaranzin, Elisabetta Zardini & Diego Franciotta

  2. Neuro-Oncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy

    Matteo Gastaldi & Elisa Vegezzi

  3. Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Otto Meyerhof Center, Heidelberg, Germany

    Sven Jarius & Brigitte Wildeman

  4. Multiple Sclerosis Centre, IRCCS Mondino Foundation, Pavia, Italy

    Giulia Mallucci & Eleonora Rigoni

  5. Pediatric Clinic, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Thomas Foiadelli & Salvatore Savasta

  6. Neurology and Stroke Unit, Circolo Hospital/Macchi Foundation, University of Insubria, Varese, Italy

    Paola Banfi & Maurizio Versino

  7. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Luana Benedetti & Giovanni Novi

  8. IRCCS Policlinico San Martino, Genoa, Italy

    Giovanni Novi

  9. Unit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department, IRCCS Istituto Giannina Gaslini, Genova, Italy

    Margherita Maria Mancardi & Thea Giacomini

  10. Multiple Sclerosis Centre, ASST Valle Olona - Gallarate Hospital, Gallarate, Italy

    Pietro Annovazzi & Damiano Baroncini

  11. Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy

    Diana Ferraro

  12. San Raffaele Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy

    Vito Lampasona

  13. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Markus Reindl

  14. Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK

    Patrick Waters

Authors
  1. Matteo Gastaldi
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  2. Silvia Scaranzin
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  3. Sven Jarius
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  22. Patrick Waters
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  23. Diego Franciotta
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Corresponding author

Correspondence to Matteo Gastaldi.

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Conflicts of interest

GM received honoraria for participation to advisory boards from Roche. The Pavia neuroimmunology laboratory receives payments for antibody assays (MOG, AQP4, and other autoantibodies) The University Hospital and Medical University of Innsbruck (Austria) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). WP and the University of Oxford hold patents and receive royalties for antibody assays. MOG antibody tests are performed in his laboratory. WP has received speaker or consulting honoraria from Alexion and UBC.

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The local ethics committee approved this study. All included patients, or their legal representatives, gave written consent for the retrospective analysis of their medical records.

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All co-authors approved the final version of this document.

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Gastaldi, M., Scaranzin, S., Jarius, S. et al. Cell-based assays for the detection of MOG antibodies: a comparative study. J Neurol 267, 3555–3564 (2020). https://doi.org/10.1007/s00415-020-10024-0

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  • DOI: https://doi.org/10.1007/s00415-020-10024-0

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