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Molecular mimicry as a potential trigger in post-vaccination MOG-seropositive NMOSD
Author(s): ,
A.-K. Pröbstel
Affiliations:
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States; Departments of Neurology & Biomedicine, University Hospital Basel and University of Basel
,
J.M. Lindner
Affiliations:
Novartis Institutes for BioMedical Research, Basel, Switzerland
,
J.J. Sabatino
Affiliations:
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
,
A.-C. Lecourt
Affiliations:
Departments of Neurology & Biomedicine, University Hospital Basel and University of Basel
,
L. Schirmer
Affiliations:
Eli and Edythe Broad Center for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA, United States
,
L. Kappos
Affiliations:
Departments of Neurology & Biomedicine, University Hospital Basel and University of Basel
,
S.E. Baranzini
Affiliations:
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
,
S.S. Zamvil
Affiliations:
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
,
E. Traggiai
Affiliations:
Novartis Institutes for BioMedical Research, Basel, Switzerland
T. Derfuss
Affiliations:
Departments of Neurology & Biomedicine, University Hospital Basel and University of Basel
ECTRIMS Online Library. Pröbstel A. Oct 12, 2018; 228918
Anne-Katrin Pröbstel
Anne-Katrin Pröbstel
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Abstract: P1077

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Immunology

Introduction: IgG (immunoglobulin G) antibodies against myelin oligodendrocyte glycoprotein (MOG) have been described in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), monophasic/recurrent optic neuritis (ON) or transverse myelitis (TM), and atypical MS. The high prevalence of anti-MOG IgG in ADEM, the manifestation of which is often preceded by vaccinations or infections, strongly suggests an environmental trigger. To date, no study has investigated the immunological link between a vaccine exposure and MOG-seropositive autoimmunity.
Objectives: Here, we investigated the immunological response against MOG and vaccine antigens in blood and cerebrospinal fluid (CSF) at a single cell level in an affected family.
Results: The index patient presented with MOG-seropositive NMOSD several weeks after vaccination, and two other individuals suffered from CNS symptoms with presence of anti-MOG antibodies. Also, the index patient had experienced ON post-vaccination a decade earlier.
Single cell expansion of B cells from the peripheral blood revealed a cross-reactive clone in the memory B cell compartment between MOG and the vaccine antigen. There was no cross-reactive clone against MOG and a vaccine antigen found in CSF. T cells were expanded from CSF by unspecific stimulation, and were screened against MOG peptides. Neither in CD4 nor in CD8 T cells a high reactivity against MOG could be detected in proliferation assays or INFg/GM-CSF ELISA. In-depth analysis of immunological and genetic assessment will be presented.
Conclusions: This is the first clinical and immunological study revealing immunological evidence for molecular mimicry as a potential mechanism for post-vaccination MOG antibody-associated demyelination. This study provides relevant insights that help identify environmental triggers of CNS autoimmunity with known and unknown antigenic targets.
Disclosure: AKP received research funding from the Swiss National Science Foundation, the National Multiple Sclerosis Society, intramural funding of the University of Basel and Genzyme, travel support from Genzyme, Baxalta and Merck and speaker honoraria from Bayer all used for research support.
JL has nothing to disclose.
JJS receives research funding from the National Institutes of Health and National MS Society. No financial conflicts of interest.
ACL has nothing to disclose.
LS received travel support from Genzyme Corporation and has filed a patent for the detection of antibodies against KIR4.1 in a subpopulation of patients with MS.
LK's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos' activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd., Sanofi, Santhera, Siemens, Teva, UCB, and Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis Research Foundation and Roche Research Foundation.
SEB received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck Serono, Biogen, Teva, Bayer-Schering, Roche, and Genzyme.
SSZ is Deputy Editor of Neurology, Neuroimmunology and Neuroinflammation and is a member of the advisory board for the International Society of Neuroimmunology. He has served on the Editorial Board of the Journal of Clinical Investigation, The Journal of Immunology and The Journal of Neurological Sciences, and has been a charter member of the grant review committee for the National Institutes of Health (NIH) Clinical Neuroimmunology and Brain Tumors (CNBT) study section and the National Multiple Sclerosis Society (NMSS). He has served as a consultant and received honoraria from Biogen-Idec, EMD-Serono, Genzyme, Novartis, Roche/Genentech, and Teva Pharmaceuticals, Inc., and has served or serves on Data Safety Monitoring Boards for Lilly, BioMS, Teva and Opexa Therapeutics. Currently, Dr. Zamvil receives research grant support from the NIH, the NMSS, The Maisin Foundation, Biogen and Celgene.
ET has nothing to disclose.
TD received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck Serono, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme.

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