Frontline: Epitope recognition on the myelin/oligodendrocyte glycoprotein differentially influences disease phenotype and antibody effector functions in autoimmune demyelination.
Preliminary observations of humoral immunity against the myelin oligodendrocyte glycoprotein (MOG) in experimental allergic encephalomyelitis (EAE) and human multiple sclerosis (MS) suggest that a subset of anti-MOG autoantibodies directed against conformational epitopes is of pathogenic predominance. Here, we provide proof that in marmoset EAE, autoantibodies reactive against conformational epitopes of MOG are not only responsible for aggravating demyelination, but also an essential factor for disease dissemination in space within the central nervous system, a hallmark for typical forms of human MS. In terms of effector mechanisms, IgG deposition and complement activation occur exclusively in association with presence of these conformational antibodies, while microglial/macrophage activation appears to be a common immunopathological finding regardless of the fine determinant specificity of anti-MOG antibodies. These findings highlight for the first time the complex heterogeneity of function and pathogenicity in the polyclonal anti-MOG antibody repertoire of outbred species. Because the linear and conformational antibody determinants of MOG are shared between marmosets and humans, these results are directly relevant to understanding effector mechanisms of organ damage in MS.
von Büdingen
Hans-Christian
HC
Department of Neurology, School of Medicine, University of California-San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.
Hauser
Stephen L
SL
Ouallet
Jean-Christophe
JC
Tanuma
Naoyuki
N
Menge
Til
T
Genain
Claude P
CP
D000818:Animals; D000906:Antibodies / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology*; D002144:Callithrix; D003711:Demyelinating Diseases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D007150:Immunohistochemistry; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
D000906:Antibodies; D000939:Epitopes; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein