Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein.

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.

• Authors: Kevin C O'Connor, Katherine A McLaughlin, Philip L De Jager, Tanuja Chitnis, Estelle Bettelli, Chenqi Xu, William H Robinson, Sunil V Cherry, Amit Bar-Or, Brenda Banwell, Hikoaki Fukaura, Toshiyuki Fukazawa, Silvia Tenembaum, Susan J Wong, Norma P Tavakoli, Zhannat Idrissova, Vissia Viglietta, Kevin Rostasy, Daniela Pohl, Russell C Dale, Mark Freedman, Lawrence Steinman, Guy J Buckle, Vijay K Kuchroo, David A Hafler, Kai W Wucherpfennig
• Journal: Nature medicine (Nat Med) Vol. 13 Issue 2 Pg. 211-7 (Feb 2007) ISSN: 1078-8956 [Print] United States
• PMID: 17237795 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• MOG protein, human
• Mog protein, mouse
• Myelin Proteins
• Myelin-Associated Glycoprotein
• Myelin-Oligodendrocyte Glycoprotein

Topics

• Animals
• Autoantibodies (immunology, isolation & purification, metabolism)
• Encephalomyelitis, Acute Disseminated (blood, immunology)
• Humans
• Immunoassay (methods)
• Mice
• Multiple Sclerosis (blood, immunology, physiopathology)
• Myelin Proteins
• Myelin-Associated Glycoprotein (immunology, metabolism)
• Myelin-Oligodendrocyte Glycoprotein
• Protein Folding
• Sensitivity and Specificity