Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein.
The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocyte glycoprotein (MOG) by selective unfolding of the antigen domain. The tetramer radioimmunoassay (RIA) was more sensitive for MOG autoantibody detection than other methodologies, including monomer-based RIA, ELISA or fluorescent-activated cell sorting (FACS). Autoantibodies from individuals with acute disseminated encephalomyelitis (ADEM) selectively bound the folded MOG tetramer, whereas sera from mice with experimental autoimmune encephalomyelitis induced with MOG peptide immunoprecipitated only the unfolded tetramer. MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS.
O'Connor
Kevin C
KC
Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
McLaughlin
Katherine A
KA
De Jager
Philip L
PL
Chitnis
Tanuja
T
Bettelli
Estelle
E
Xu
Chenqi
C
Robinson
William H
WH
Cherry
Sunil V
SV
Bar-Or
Amit
A
Banwell
Brenda
B
Fukaura
Hikoaki
H
Fukazawa
Toshiyuki
T
Tenembaum
Silvia
S
Wong
Susan J
SJ
Tavakoli
Norma P
NP
Idrissova
Zhannat
Z
Viglietta
Vissia
V
Rostasy
Kevin
K
Pohl
Daniela
D
Dale
Russell C
RC
Freedman
Mark
M
Steinman
Lawrence
L
Buckle
Guy J
GJ
Kuchroo
Vijay K
VK
Hafler
David A
DA
Wucherpfennig
Kai W
KW
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D004673:Encephalomyelitis, Acute Disseminated / Q000097:blood / Q000276:immunology*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D051379:Mice; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D017510:Protein Folding; D012680:Sensitivity and Specificity
D001323:Autoantibodies; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein