1. MOG Antibody Pathogenicity
- Author
-
Spadaro, M., Winklmeier, S., Beltrán, E., Macrini, C., Höftberger, R., Schuh, E., Thaler, F.S., Gerdes, L.A., Laurent, S.A., Gerhards, R., Brändle, S., Dornmair, K., Breithaupt, C., Krumbholz, M., Moser, M., Kirshnamoorthy, G., Kamp, F., Jenne, D., Hohlfeld, R., Kümpfel, T., Lassmann, H., Kawakami, N., and Meinl, E.
- Subjects
Adult ,Inflammation ,Male ,Encephalomyelitis, Autoimmune, Experimental ,Guinea Pigs ,Brain ,Middle Aged ,nervous system diseases ,Rats ,Young Adult ,nervous system ,immune system diseases ,Rats, Inbred Lew ,Animals ,Humans ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Aged ,Autoantibodies - Abstract
ObjectiveAutoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with inflammatory demyelinating diseases of the central nervous system (CNS). We analyzed their pathogenic activity by affinity-purifying these antibodies (Abs) from patients and transferring them to experimental animals.MethodsPatients with Abs to MOG were identified by cell-based assay. We determined the cross-reactivity to rodent MOG and the recognized MOG epitopes. We produced the correctly folded extracellular domain of MOG and affinity-purified MOG-specific Abs from the blood of patients. These purified Abs were used to stain CNS tissue and transferred in 2 models of experimental autoimmune encephalomyelitis. Animals were analyzed histopathologically.ResultsWe identified 17 patients with MOG Abs from our outpatient clinic and selected 2 with a cross-reactivity to rodent MOG; both had recurrent optic neuritis. Affinity-purified Abs recognized MOG on transfected cells and stained myelin in tissue sections. The Abs from the 2 patients recognized different epitopes on MOG, the CC and the FG loop. In both patients, these Abs persisted during our observation period of 2 to 3 years. The anti-MOG Abs from both patients were pathogenic upon intrathecal injection in 2 different rat models. Together with cognate MOG-specific T cells, these Abs enhanced T-cell infiltration; together with myelin basic protein-specific T cells, they induced demyelination associated with deposition of C9neo, resembling a multiple sclerosis type II pathology.InterpretationMOG-specific Abs affinity purified from patients with inflammatory demyelinating disease induce pathological changes in vivo upon cotransfer with myelin-reactive T cells, suggesting that these Abs are similarly pathogenic in patients. Ann Neurol 2018;84:315-328
- Published
- 2018