1. Academic Validation
  2. 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. sara.mariotto@gmail.com.
  • 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.
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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