Supplemental material for MOG-IgG-associated disease has a stereotypical clinical course, asymptomatic visual impairment and good treatment response

<p>Supplemental material for MOG-IgG-associated disease has a stereotypical clinical course, asymptomatic visual impairment and good treatment response by Lekha Pandit, Sharik Mustafa, Ichiro Nakashima, Toshyuki Takahashi and Kimhiko Kaneko in Multiple Sclerosis Journal – Experimental, Translational and Clinical</p

Image_5_Complement-dependent cytotoxicity of human autoantibodies against myelin oligodendrocyte glycoprotein.TIF

BackgroundThe autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody.ObjectiveTo elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells.MethodsMammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry.ResultsAmong 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors.ConclusionThe human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.</p

Image_6_Complement-dependent cytotoxicity of human autoantibodies against myelin oligodendrocyte glycoprotein.TIF

BackgroundThe autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody.ObjectiveTo elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells.MethodsMammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry.ResultsAmong 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors.ConclusionThe human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.</p

Image_1_Complement-dependent cytotoxicity of human autoantibodies against myelin oligodendrocyte glycoprotein.TIF

BackgroundThe autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody.ObjectiveTo elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells.MethodsMammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry.ResultsAmong 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors.ConclusionThe human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.</p

Table_1_Complement-dependent cytotoxicity of human autoantibodies against myelin oligodendrocyte glycoprotein.DOCX

BackgroundThe autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody.ObjectiveTo elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells.MethodsMammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry.ResultsAmong 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors.ConclusionThe human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.</p

Structure−function relationships in eyes with single-episode optic neuritis.

<p>Scatter plots of mean deviation (MD) against circumpapillary retinal nerve fiber layer (RNFL) average thickness (A), MD against ganglion cell complex (GCC) thickness (B), logMAR visual acuity (VA) against circumpapillary RNFL average thickness (C), and VA against GCC average thickness (D). Open circles and dotted lines indicate eyes with aquaporin 4 antibody (AQP4 Ab)-negative optic neuritis, whereas closed circles and solid lines indicate eyes with antibody-positive optic neuritis. Spearman rank correlation coefficients (95% confidence interval, P-value) for the antibody-negative and -positive groups were 0.39 (-0.24 to 0.79, 0.22) and 0.75 (0.27 to 0.93, 0.008), respectively, between MD and average RNFL thickness (A), 0.58 (0.01 to 0.87, 0.05) and 0.77 (0.32 to 0.94, 0.006), respectively, between MD and average GCC thickness (B), -0.47 (-0.82 to 0.14, 0.12) and -0.39 (-0.80 to 0.28, 0.24), respectively, between logMAR VA and average RNFL thickness (C), and -0.65 (-0.89 to -0.11, 0.02) and -0.62 (-0.89 to -0.02, 0.04), respectively, between logMAR VA and average GCC thickness (D).</p