TY - JOUR
T1 - Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton
AU - Dale, Russell C.
AU - Tantsis, Esther M.
AU - Merheb, Vera
AU - Kumaran, Raani Yogeeta A.
AU - Sinmaz, Nese
AU - Pathmanandavel, Karrnan
AU - Ramanathan, Sudarshini
AU - Booth, David R.
AU - Wienholt, Louise A.
AU - Prelog, Kristina
AU - Clark, Damien R.
AU - Guillemin, Gilles J.
AU - Lim, Chai K.
AU - Mathey, Emily K.
AU - Brilot, Fabienne
N1 - Copyright the Author(s) 2014. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2014/4/24
Y1 - 2014/4/24
N2 - OBJECTIVE: To examine the clinical features of pediatric CNS demyelination associated with positive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects of MOG antibody on oligodendrocyte cytoskeleton.METHODS: We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3-15.3) followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on oligodendrocyte cytoskeleton using 3D deconvolution imaging.RESULTS: MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first presentation, MOG antibody-positive patients were more likely to have bilateral than unilateral optic neuritis (ON) (9/10 vs 1/5, respectively, p = 0.03), less likely to have brainstem findings (2/31 vs 16/42, p = 0.005), more likely to have a raised erythrocyte sedimentation rate >20 mm/h (9/19 vs 3/21, p = 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p = 0.18), and less likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, p = 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON most likely to be seropositive. Two relapsing MOG antibody-positive patients treated with mycophenolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes incubated with purified IgG from MOG antibody-positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and β-tubulin immunolabelings.CONCLUSIONS: MOG antibody may define a separate demyelination syndrome, which has therapeutic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton.
AB - OBJECTIVE: To examine the clinical features of pediatric CNS demyelination associated with positive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects of MOG antibody on oligodendrocyte cytoskeleton.METHODS: We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3-15.3) followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on oligodendrocyte cytoskeleton using 3D deconvolution imaging.RESULTS: MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first presentation, MOG antibody-positive patients were more likely to have bilateral than unilateral optic neuritis (ON) (9/10 vs 1/5, respectively, p = 0.03), less likely to have brainstem findings (2/31 vs 16/42, p = 0.005), more likely to have a raised erythrocyte sedimentation rate >20 mm/h (9/19 vs 3/21, p = 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p = 0.18), and less likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, p = 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON most likely to be seropositive. Two relapsing MOG antibody-positive patients treated with mycophenolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes incubated with purified IgG from MOG antibody-positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and β-tubulin immunolabelings.CONCLUSIONS: MOG antibody may define a separate demyelination syndrome, which has therapeutic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton.
UR - http://www.scopus.com/inward/record.url?scp=84922955744&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000012
DO - 10.1212/NXI.0000000000000012
M3 - Article
C2 - 25340056
SN - 2332-7812
VL - 1
SP - 1
EP - 12
JO - Neurology: Neuroimmunology and Neuroinflammation
JF - Neurology: Neuroimmunology and Neuroinflammation
IS - 1
M1 - e12
ER -