2. Academic Validation
  3. Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases

Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases

  • Neurology. 2019 Nov 12;93(20):e1867-e1872. doi: 10.1212/WNL.0000000000008479.
Sara Mariotto 1,  Alberto Gajofatto 2,  Lucia Batzu 2,  Rachele Delogu 2,  GianPietro Sechi 2,  Stefania Leoni 2,  Maria Immacolata Pirastru 2,  Bruno Bonetti 2,  Mattia Zanoni 2,  Daniela Alberti 2,  Kathrin Schanda 2,  Salvatore Monaco 2,  Markus Reindl 2,  Sergio Ferrari 2
Affiliations

Affiliations

  • 1 From the Section of Neurology (S.M., A.G., M.Z., D.A., S.M., S.F.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona; Neurology Unit (L.B., R.D., G.S., S.L., M.I.P.), Department of Medical, Surgical, and Experimental Sciences, University of Sassari; Neurology Unit (B.B.), AOUI Verona, Italy; and Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria. [email protected].
  • 2 From the Section of Neurology (S.M., A.G., M.Z., D.A., S.M., S.F.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona; Neurology Unit (L.B., R.D., G.S., S.L., M.I.P.), Department of Medical, Surgical, and Experimental Sciences, University of Sassari; Neurology Unit (B.B.), AOUI Verona, Italy; and Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria.
PMID: 31645473 DOI: 10.1212/WNL.0000000000008479
Abstract

Objective: To determine the diagnostic relevance of myelin oligodendrocyte glycoprotein Antibodies (MOG-Abs) in CSF of seronegative cases by retrospectively analyzing consecutive time-matched CSF of 80 MOG-Ab-seronegative patients with demyelinating disease.

Methods: The cohort included 44 patients with NMOSD and related disorders and 36 patients with multiple sclerosis (MS). Two independent neurologists blinded to diagnosis analyzed MOG-Abs by live cell-based immunofluorescence assay with goat anti-human immunoglobulin (Ig) G (whole molecule) antibody. Sera were tested at dilutions of 1:20 and 1:40, and a cutoff of 1:160 was considered for serum positivity. CSF specimens were tested undiluted and at 1:2 dilution with further titrations in case of positivity. Anti-IgG-Fc and anti-IgM-µ secondary Antibodies were used to confirm the exclusive presence of MOG-IgG in positive cases. CSF of 13 MOG-Abs seropositive cases and 36 patients with neurodegenerative conditions was analyzed as controls.

Results: Three seronegative cases had CSF MOG-Abs (4% of the whole cohort or 7% of cases excluding patients with MS, in which MOG-Abs seem to lack diagnostic relevance). In particular, 2 patients with neuromyelitis optica spectrum disorder (NMOSD) and 1 with acute disseminated encephalomyelitis had MOG-Abs in CSF. Analysis with anti-IgG-Fc and anti-IgM confirmed the exclusive presence of MOG-IgG in the CSF of these patients. Among the control group, MOG-Abs were detectable in the CSF of 8 of 13 MOG-Ab-seropositive cases and in none of the patients with neurodegenerative disorders.

Conclusion: Although serum is the optimal specimen for MOG-Ab testing, analyzing CSF could improve diagnostic sensitivity in seronegative patients. This observation has relevant diagnostic impact and might provide novel insight into the biological mechanisms of MOG-Ab synthesis.

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