Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein

Spadaro, Melania; Winklmeier, Stephan; Beltran, Eduardo; Macrini, Caterina; Hoeftberger, Romana; Schuh, Elisabeth; Thaler, Franziska S.; Gerdes, Lisa Ann; Laurent, Sarah; Gerhards, Ramona; Braendle, Simone; Dornmair, Klaus; Breithaupt, Constanze; Krumbholz, Markus; Moser, Markus; Krishnamoorthy, Gurumoorthy; Kamp, Frits; Jenne, Dieter; Hohlfeld, Reinhard; Kuempfel, Tania; Lassmann, Hans; Kawakami, Naoto und Meinl, Edgar (2018): Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. In: Annals of Neurology, Bd. 84, Nr. 2: S. 315-328

Abstract

Objective: Autoantibodies 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. Methods: Patients 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. Results: We 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

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0364-5134
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198