Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein |
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Authors: | O'Connor Kevin C McLaughlin Katherine A De Jager Philip L Chitnis Tanuja Bettelli Estelle Xu Chenqi Robinson William H Cherry Sunil V Bar-Or Amit Banwell Brenda Fukaura Hikoaki Fukazawa Toshiyuki Tenembaum Silvia Wong Susan J Tavakoli Norma P Idrissova Zhannat Viglietta Vissia Rostasy Kevin Pohl Daniela Dale Russell C Freedman Mark Steinman Lawrence Buckle Guy J Kuchroo Vijay K Hafler David A Wucherpfennig Kai W |
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Institution: | Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. |
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Abstract: | 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. |
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