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Letter
Neurofilament light chain serum levels reflect disease severity in MOG-Ab associated disorders
  1. Sara Mariotto1,
  2. Sergio Ferrari1,
  3. Matteo Gastaldi2,
  4. Diego Franciotta2,
  5. Elia Sechi3,
  6. Ruggero Capra4,
  7. Chiara Mancinelli4,
  8. Kathrin Schanda5,
  9. Daniela Alberti6,
  10. Riccardo Orlandi7,
  11. Roberto Bombardi8,
  12. Luigi Zuliani9,
  13. Marco Zoccarato10,
  14. Maria Donata Benedetti11,
  15. Raffaella Tanel12,
  16. Francesca Calabria13,
  17. Francesca Rossi14,
  18. Antonino Pavone15,
  19. Luisa Grazian16,
  20. GianPietro Sechi17,
  21. Lucia Batzu18,
  22. Noemi Murdeu19,
  23. Francesco Janes20,
  24. Vincenza Fetoni21,
  25. Daniela Fulitano22,
  26. Gianola Stenta23,
  27. Lisa Federle23,
  28. Gaetano Cantalupo24,
  29. Markus Reindl25,
  30. Salvatore Monaco26,
  31. Alberto Gajofatto1
  1. 1 Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  2. 2 Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy, Pavia, Italy
  3. 3 Department of Clinical and Experimental Medicine, Neurology Unit, University of Sassari, Sassari, Italy
  4. 4 MS Center, Spedali Civili of Brescia, Brescia, Italy
  5. 5 Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  6. 6 Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  7. 7 Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  8. 8 Neurology Unit, San Bassiano Hospital, Bassano Del Grappa, Italy
  9. 9 Department of Neurology, Ospedale Ca’ Foncello, Treviso, Italy
  10. 10 O.S.A, Padova, Italy, Neurology Unit, Padova, Italy
  11. 11 Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  12. 12 U.O. Neurologia, S. Chiara Hospital, Trento, Italy
  13. 13 AOUI Verona, Neurology Unit, Verona, Italy
  14. 14 Neurology Unit, Mater Salutis Hospital, Legnago, Verona, Italy, Verona, Italy
  15. 15 Neurology Unit, Garibaldi Hospital, Catania, Italy, Catania, Italy
  16. 16 Pediatric Unit, ULSS 2 Marca Trevigiana, Ca' Foncello Hospital, Treviso, Italy, Treviso, Italy
  17. 17 Department of Clinical and Experimental Medicine, NeurologyUnit, University of Sassari, Sassari, Italy
  18. 18 Department of Clinical and Experimental Medicine, Neurology Unit, University of Sassari, Sassari, Italy
  19. 19 Department of Clinical and Experimental Medicine, Neurology Unit, University of Sassari, Sassari, Italy
  20. 20 Neurology Unit, Department of Neuroscience ASUIUD, Udine, Italy, Udine, Italy
  21. 21 Neurology Department, ASST Fatebenefratelli Sacco, Milano, Italy, Milano, Italy
  22. 22 Neurology Unit, Rovigo, Italy, Rovigo, Italy
  23. 23 Multiple Sclerosis Centre, S. Bortolo Hospital, Vicenza, Italy, Vicenza, Italy
  24. 24 Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
  25. 25 Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  26. 26 Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Neurology, University of Verona, Verona, Italy
  1. Correspondence to Dr Sara Mariotto, Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, Verona 37134, Italy; sara.mariotto{at}gmail.com

https://doi.org/10.1136/jnnp-2018-320287

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    Introduction

    The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in sera of subjects with inflammatory central nervous system (CNS) conditions has improved the differential diagnosis between multiple sclerosis (MS) and antibody-mediated demyelinating disorders.1 However, the heterogeneous clinical course of MOG-Ab-positive cases complicates outcome prediction. Cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels reliably predict disease activity in patients with clinically isolated syndrome and MS.2

    We assessed serum and CSF NfL concentration in patients with MOG-Ab-associated conditions according to clinical/paraclinical characteristics to investigate NfL as a biomarker of disease severity.

    Materials and methods

    Between 2015 and 2018, we included 38 consecutive MOG-Ab-positive patients tested at our institution and 38 age-matched unaffected controls.

    Clinical data at sampling and at last follow-up, MRI and CSF findings were collected in standardised case report forms. Brain/spinal cord MRIs were obtained within 2 months from blood drawn for MOG-Ab/NfL analysis and assessed by referring neurologists blinded to assay results.

    Blood samples were collected, centrifuged and stored at −80°C. Presence of serum AQP4-Ab was analysed using a commercial cell-based assay (Euroimmun, Lübeck, Germany). Two independent investigators analysed MOG-Ab using recombinant live cell-based immunofluorescence assay with HEK293A cells transfected with full-length MOG (human MOG alpha-1 EGFP fusion protein), as previously described.3

    Investigators blinded to clinical data performed NfL analysis in all sera and, when available, in CSF samples. Sera/CSF of MOG-Ab-positive cases were obtained during the index attack, with the exception of two patients asymptomatic at sampling. Measurement of NfL concentration was analysed in duplicates using SIMOA Nf-light kit with SR-X immunoassay analyser (Quanterix, Boston, Massachusetts, USA) which runs ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assays.

    Statistical analysis

    Continuous/categorical variables were reported as median (range) and percentages, respectively. Mann-Whitney U test and Wilcoxon signed-rank test were used for pairwise comparison of NfL levels within and between groups, as appropriate according …

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    Footnotes

    • Presented at The data here reported have been presented at the ECTRIMS and EAN annual meeting, 2018.

    • Contributors SMA: sample collection, analysis and interpretation of MOG-Ab, AQP4-Ab and NfL results, design and conceptualisation of the study, data generation and interpretation, drafting the manuscript. SF: sample collection, interpretation of MOG-Ab, AQP4-Ab and NfL, design of the study. MG and DFR: interpretation of MOG and AQP4-Ab, collection and interpretation of clinical data. ES, RC, CRM, RO, RB, LZ, MZ, MDB, RT, FC, FR, AP, LG, GPS, LB, NM, FJ, VF, DFU, GS, LF, GC: collection and interpretation of clinical data. KS: analysis and interpretation of MOG-Ab and AQP4-Ab. DA: analysis and interpretation of MOG-Ab, AQP4-Ab, and NfL. MR: interpretation of MOG-Ab and AQP4-Ab, revising the manuscript for intellectual content. SMO: data interpretation and revising the manuscript for intellectual content. AG: statistical analysis, data generation, collection and interpretation of clinical data, design of the study.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sector.

    • Competing interests SMA was sponsored by Merck and Euroimmun for attending scientific meeting. SF was sponsored by Shire and Euroimmun for attending scientific meeting. RC received lecture fees and/or travel grants from Novartis, Biogen, Celgene, Novartis, TEVA, Genzyme and Sanofi-Aventis. MR was supported by a research grant from the Austrian Science Promotion Agency (FFG). The University Hospital and Medical University of Innsbruck (Austria; MR) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organised by Euroimmun (Lübeck, Germany). SMO received honoraria from Biogen. AG received research support funding from Merck.

    • Patient consent for publication Not required.

    • Ethics approval The study protocol was approved by the Ethics Committee of Verona University Hospital (prog. 1052CESC Verona-Rovigo). All patients and controls consented to biological sample storage at the referring laboratory.

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

    • Data sharing statement The authors agree to share any unpublished data related to this study, which can be asked from the corresponding author.