MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity

Abstract

KCO has received research support from Alexion (part of AstraZeneca), Viela Bio (part of Horizon Therapeutics), Cabaletta Bio, and argenx. KCO is a consultant and equity shareholder of Cabaletta Bio. KCO has served as consultant/advisor for Alexion and Roche. EEL receives research support from Genentech and has served as a consultant for Genentech, Janssen, TG Therapeutics, NGM Bio, EMD Serono, Genzyme, and Bristol Myers Squibb. JMT receives royalties from Alexion and is a consultant for Q32 Bio, a company developing complement inhibitors. He holds stock in and will receive royalty income from Q32 Bio. RJN has received consultancy fees from Alexion, argenx, CSL Behring, Grifols, Immunovant, Momenta (part of Janssen), Ra Pharmaceuticals (part of UCB), and Viela Bio. CFL may accrue revenue for a patent regarding aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica, and receives research support from the National MS Society, Biogen,

MOG CNS Autoimmunity and MOGAD

“…Antibodies from patients with MOGAD can induce these effector functions when exposed in vitro to cells expressing full-length MOG. 13 MOG is exposed on the outer oligodendrocyte surface, possibly permitting antibody exposure to this target antigen. 14 However, current data supporting the pathogenicity of anti-MOG antibodies in vivo is indirect: IgG staining is present in some MOGAD lesions, MOG IgG can be detected in the CSF of many patients with MOGAD, and MOG antibody titers are often elevated around the time of an attack.…”

“… 15 Unlike AQP4-specific IgG1 from patients with NMO, MOG-specific IgG1 from patients with MOGAD may preferentially bind MOG in a bivalent manner that is less efficient for recruitment of C1q and activation of CDC 12 but may promote ADCC or ADCP. 13 Natural killer cell (NK); myeloid APC (M). Copyright Xavier Studio, reprinted with permission.…”

The Role of the Intestinal Microbiome in Multiple Sclerosis—Lessons to Be Learned from Hippocrates

“…Although it is unclear if the presence of follicles causes the severe disease or if it is rather the consequence of disease progression, the association between follicle formation and disease progression has been noted, [26,27]. Accordingly, immune cells are found to be autoreactive against myelin basic protein and proteolipid protein, components of the myelin sheets, and immunohistochemistry analyses identified C3d-, C9-and IgG-coated oligodendrocytes in the CNS of MS patients [28][29][30]. The role of…”

“…Although it is unclear if the presence of follicles causes the severe disease or if it is rather the consequence of disease progression, the association between follicle formation and disease progression has been noted, [26,27]. Accordingly, immune cells are found to be autoreactive against myelin basic protein and proteolipid protein, components of the myelin sheets, and immunohistochemistry analyses identified C3d-, C9-and IgG-coated oligodendrocytes in the CNS of MS patients [28][29][30]. The role of autoreactive immune cells in the pathogenesis of the neuroinflammation in the CNS of MS patients has been supported by the findings that myelin basic protein-activated CD5 + T cells are able to provoke experimental allergic encephalomyelitis in healthy mice and that HLA-DR-positive macrophages are also present in the CSF of MS patients [31,32].…”