Display options
Cite
Keller CW, Lopez JA, Wendel EM, et al. Complement Activation Is a Prominent Feature of MOGAD. Ann Neurol. 2021;90(6):976-982doi: 10.1002/ana.26226.
Keller, C. W., Lopez, J. A., Wendel, E. M., Ramanathan, S., Gross, C. C., Klotz, L., Reindl, M., Dale, R. C., Wiendl, H., Rostásy, K., Brilot, F., & Lünemann, J. D. (2021). Complement Activation Is a Prominent Feature of MOGAD. Annals of neurology, 90(6), 976-982. https://doi.org/10.1002/ana.26226
Keller, Christian W, et al. "Complement Activation Is a Prominent Feature of MOGAD." Annals of neurology vol. 90,6 (2021): 976-982. doi: https://doi.org/10.1002/ana.26226
Keller CW, Lopez JA, Wendel EM, Ramanathan S, Gross CC, Klotz L, Reindl M, Dale RC, Wiendl H, Rostásy K, Brilot F, Lünemann JD. Complement Activation Is a Prominent Feature of MOGAD. Ann Neurol. 2021 Dec;90(6):976-982. doi: 10.1002/ana.26226. Epub 2021 Oct 09. PMID: 34569094.
Copy Download .nbib Format: NLM
Share it on

Ann Neurol. 2021 Dec;90(6):976-982. doi: 10.1002/ana.26226. Epub 2021 Oct 09.

Complement Activation Is a Prominent Feature of MOGAD.

Annals of neurology

Christian W Keller, Joseph A Lopez, Eva-Maria Wendel, Sudarshini Ramanathan, Catharina C Gross, Luisa Klotz, Markus Reindl, Russell C Dale, Heinz Wiendl, Kevin Rostásy, Fabienne Brilot, Jan D Lünemann

Affiliations

  1. Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
  2. Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, New South Wales, Australia.
  3. Discipline of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  4. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  5. Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
  6. Department of Pediatrics, Olgahospital/Klinikum Stuttgart, Stuttgart, Germany.
  7. Department of Neurology, Concord Hospital, Sydney, New South Wales, Australia.
  8. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
  9. Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany.

PMID: 34569094 DOI: 10.1002/ana.26226

Abstract

Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated diseases (MOGADs) account for a substantial proportion of pediatric and adult patients who present with acquired demyelinating disorders. Its pathogenesis and optimal therapy are incompletely understood. We profiled systemic complement activation in adult and pediatric patients with MOGAD compared with patients with relapse-onset multiple sclerosis, patients with neuromyelitis optica spectrum disorder, and pediatric control and adult healthy donors. Proteins indicative of systemic classical and alternative complement activation were substantially increased in patients with MOGAD compared to control groups. Elevated levels were detected in both adult and pediatric cases and across all clinical syndromes. Complement inhibition should be explored for its therapeutic merit in patients with MOGAD. ANN NEUROL 2021;90:976-982.

© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

References

  1. Whittam DH, Cobo-Calvo A, Lopez-Chiriboga AS, et al. Treatment of MOG-IgG-associated disorder with rituximab: an international study of 121 patients. Mult Scler Relat Disord 2020;44:102251. - PubMed
  2. Gavriilaki E, Brodsky RA. Complementopathies and precision medicine. J Clin Invest 2020;130:2152-2163. - PubMed
  3. Soltys J, Liu Y, Ritchie A, et al. Membrane assembly of aquaporin-4 autoantibodies regulates classical complement activation in neuromyelitis optica. J Clin Invest 2019;129:2000-2013. - PubMed
  4. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in Aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 2019;381:614-625. - PubMed
  5. Reindl M, Schanda K, Woodhall M, et al. International multicenter examination of MOG antibody assays. Neurol Neuroimmunol Neuroinflamm 2020;7:e674. - PubMed
  6. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-189. - PubMed
  7. Gaya da Costa M, Poppelaars F, van Kooten C, et al. Age and sex-associated changes of complement activity and complement levels in a healthy Caucasian population. Front Immunol 2018;9:2664. - PubMed
  8. Sanders ME, Koski CL, Robbins D, et al. Activated terminal complement in cerebrospinal fluid in Guillain-Barré syndrome and multiple sclerosis. J Immunol 1986;136:4456-4459. - PubMed
  9. Jongen PJ, Doesburg WH, Ibrahim-Stappers JL, et al. Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system. Acta Neurol Scand 2000;101:116-121. - PubMed
  10. Bhargava P, Nogueras-Ortiz C, Kim S, et al. Synaptic and complement markers in extracellular vesicles in multiple sclerosis. Mult Scler 2019;2020:509-518. - PubMed
  11. Nytrova P, Potlukova E, Kemlink D, et al. Complement activation in patients with neuromyelitis optica. J Neuroimmunol 2014;274:185-191. - PubMed
  12. Hakobyan S, Luppe S, Evans DR, et al. Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder. Mult Scler 2017;23:946-955. - PubMed
  13. Lucchinetti C, Brück W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-717. - PubMed
  14. Pache F, Ringelstein M, Aktas O, et al. C3 and C4 complement levels in AQP4-IgG-positive NMOSD and in MOGAD. J Neuroimmunol 2021;360:577699. - PubMed
  15. Höftberger R, Guo Y, Flanagan EP, et al. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol 2020;139:875-892. - PubMed
  16. Takai Y, Misu T, Kaneko K, et al. Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study. Brain 2020;143:1431-1446. - PubMed
  17. Liu J, Mori M, Zimmermann H, et al. Anti-MOG antibody-associated disorders: differences in clinical profiles and prognosis in Japan and Germany. J Neurol Neurosurg Psychiatry 2020;92:377-383. - PubMed
  18. Tea F, Lopez JA, Ramanathan S, et al. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination. Acta Neuropathol Commun 2019;7:145-122. - PubMed
  19. Dale RC, Tantsis EM, Merheb V, et al. Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurol Neuroimmunol Neuroinflamm 2014;1:e12. - PubMed
  20. Piddlesden SJ, Lassmann H, Zimprich F, et al. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol 1993;143:555-564. - PubMed
  21. Spadaro M, Winklmeier S, Beltrán E, et al. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol 2018;84:315-328. - PubMed
  22. Holers VM. Complement and its receptors: new insights into human disease. Annu Rev Immunol 2014;32:433-459. - PubMed

Publication Types

Grant support