Contributions
Abstract: P306
Type: Poster
Abstract Category: Clinical aspects of MS - 2 MS Variants
Background: Recent studies indicate Anti-Myelin Oligodendrocyte Glycoprotein antibodies (MOG- IgG) as new serum biomarker of some forms of demyelinating diseases distinct both from classical Multiple sclerosis (MS) and from AQP4-IgG-mediated neuromyelitis optica spectrum disorders (NMOSD).
Aims and methods: The aims of this study were 1) to evaluate, by a Cell Based Assay on HEK-293 cells stably transfected with human MOG, the frequency of serum MOG-IgG in a cohort of 57 adult patients with a first monosymptomatic episode of idiopathic autoimmune Optic Neuritis (ON) or Myelitis prospectively followed for a median period of 3.3±3.2 years; 2) to compare baseline clinical, laboratory and MRI features of patients with and without serum MOG-IgG; 3) to investigate the potential cytotoxic effect of MOG-IgG, obtained by immunoadsorption, on ex vivo rat optic nerve. Rat optic nerve was cultured on transwell porous supports for 24 h in CO2/O2-bubbled artificial cerebrospinal fluid (CSF), with human complement (HC) and/or MOG-IgG.
Results: Nineteen patients (33%) showed serum anti-MOG-IgG: 11 myelitis and 8 ON. MOG-IgG positive patients were older (p=0.001), had more severe disability at onset (p=0.0001), lower incidence of CSF IgG oligoclonal bands (31% vs 73%; p=0.003), lower number of brain MRI lesions (p=0.0001) and higher frequency of longer MRI spinal cord lesions (36% vs 5%; p=0.001) in comparison to MOG-IgG negative subjects. At follow-up, 42% of MOG-IgG positive patients satisfied MRI criteria for MS diagnosis vs 65% of MOG-IgG negative (p=0.07).
Rat optic nerve exposure to MOG-IgG and HC produced marked loss of myelin as a consequence of an oligodendrocytic damage, whereas astrocytes were not involved as demonstrated by normal Glial Fibrillary Acid Protein (GFAP) and AQP4 expression levels. No damages were seen in rat optic nerve cultured with either MOG-IgG or complement alone.
Conclusions: The peculiar clinical and paraclinical characteristics of MOG-IgG positive patients with ON and myelitis and the demonstrated complement-mediated cytotoxic effect of MOG-IgG on rat optic nerve oligodendrocytes, suggest that MOG autoimmunity is associated to an oligodendrocytes-mediated disease more similar clinically to NMOSD and pathologically to a pattern II variant of MS. Such a hypothesis warrant therapeutical considerations.
Disclosure:
C Tortorella received honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
Vita Di Renzo, Claudia Palazzo, Antonio Cibelli, Elena Luciannatelli, Mariangela Mastrapasqua, Maddalena Ruggieri, Paola Nicchia and Antonio Frigeri have nothing to disclose.
Damiano Paolicelli received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Almirall, Sanofi-Aventis, TEVA, Novartis and Genzyme.
Pietro Iaffaldano has served on scientific advisory boards for Biogen Idec and Novartis, and has received funding for travel and/or speaker honoraria from Genzyme, Biogen Idec, Merck-serono, Teva and Novartis.
Maria Trojano has served on scientific advisory boards and has received funding for travel and/or speaker honoraria for Biogen Idec, Genzyme, Teva, Merck-Serono, Roche, Almirall and Novartis.
Abstract: P306
Type: Poster
Abstract Category: Clinical aspects of MS - 2 MS Variants
Background: Recent studies indicate Anti-Myelin Oligodendrocyte Glycoprotein antibodies (MOG- IgG) as new serum biomarker of some forms of demyelinating diseases distinct both from classical Multiple sclerosis (MS) and from AQP4-IgG-mediated neuromyelitis optica spectrum disorders (NMOSD).
Aims and methods: The aims of this study were 1) to evaluate, by a Cell Based Assay on HEK-293 cells stably transfected with human MOG, the frequency of serum MOG-IgG in a cohort of 57 adult patients with a first monosymptomatic episode of idiopathic autoimmune Optic Neuritis (ON) or Myelitis prospectively followed for a median period of 3.3±3.2 years; 2) to compare baseline clinical, laboratory and MRI features of patients with and without serum MOG-IgG; 3) to investigate the potential cytotoxic effect of MOG-IgG, obtained by immunoadsorption, on ex vivo rat optic nerve. Rat optic nerve was cultured on transwell porous supports for 24 h in CO2/O2-bubbled artificial cerebrospinal fluid (CSF), with human complement (HC) and/or MOG-IgG.
Results: Nineteen patients (33%) showed serum anti-MOG-IgG: 11 myelitis and 8 ON. MOG-IgG positive patients were older (p=0.001), had more severe disability at onset (p=0.0001), lower incidence of CSF IgG oligoclonal bands (31% vs 73%; p=0.003), lower number of brain MRI lesions (p=0.0001) and higher frequency of longer MRI spinal cord lesions (36% vs 5%; p=0.001) in comparison to MOG-IgG negative subjects. At follow-up, 42% of MOG-IgG positive patients satisfied MRI criteria for MS diagnosis vs 65% of MOG-IgG negative (p=0.07).
Rat optic nerve exposure to MOG-IgG and HC produced marked loss of myelin as a consequence of an oligodendrocytic damage, whereas astrocytes were not involved as demonstrated by normal Glial Fibrillary Acid Protein (GFAP) and AQP4 expression levels. No damages were seen in rat optic nerve cultured with either MOG-IgG or complement alone.
Conclusions: The peculiar clinical and paraclinical characteristics of MOG-IgG positive patients with ON and myelitis and the demonstrated complement-mediated cytotoxic effect of MOG-IgG on rat optic nerve oligodendrocytes, suggest that MOG autoimmunity is associated to an oligodendrocytes-mediated disease more similar clinically to NMOSD and pathologically to a pattern II variant of MS. Such a hypothesis warrant therapeutical considerations.
Disclosure:
C Tortorella received honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
Vita Di Renzo, Claudia Palazzo, Antonio Cibelli, Elena Luciannatelli, Mariangela Mastrapasqua, Maddalena Ruggieri, Paola Nicchia and Antonio Frigeri have nothing to disclose.
Damiano Paolicelli received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Almirall, Sanofi-Aventis, TEVA, Novartis and Genzyme.
Pietro Iaffaldano has served on scientific advisory boards for Biogen Idec and Novartis, and has received funding for travel and/or speaker honoraria from Genzyme, Biogen Idec, Merck-serono, Teva and Novartis.
Maria Trojano has served on scientific advisory boards and has received funding for travel and/or speaker honoraria for Biogen Idec, Genzyme, Teva, Merck-Serono, Roche, Almirall and Novartis.