Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein.
Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading.
O'Connor
Kevin C
KC
Department of Neurology and Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. koconnor@rics.bwh.harvard.edu
Appel
Heiner
H
Bregoli
Lisa
L
Call
Matthew E
ME
Catz
Ingrid
I
Chan
Jennifer A
JA
Moore
Nicole H
NH
Warren
Kenneth G
KG
Wong
Susan J
SJ
Hafler
David A
DA
Wucherpfennig
Kai W
KW
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000302:isolation & purification / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology; D005260:Female; D015200:Fluoroimmunoassay / Q000379:methods; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011863:Radioimmunoassay / Q000379:methods; D012996:Solutions
D001323:Autoantibodies; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012996:Solutions