Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases

Schanda, Kathrin; Peschl, Patrick; Lerch, Magdalena; Seebacher, Barbara; Mindorf, Swantje; Ritter, Nora; Probst, Monika; Hegen, Harald; Di Pauli, Franziska; Wendel, Eva-Maria; Lechner, Christian; Baumann, Matthias; Mariotto, Sara; Ferrari, Sergio; Saiz, Albert; Farrell, Michael; Leite, Maria Isabel S.; Irani, Sarosh R.; Palace, Jacqueline; Lutterotti, Andreas; Kuempfel, Tania; Vukusic, Sandra; Marignier, Romain; Waters, Patrick; Rostasy, Kevin; Berger, Thomas; Probst, Christian; Hoeftberger, Romana und Reindl, Markus (2021): Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases. In: Neurology-Neuroimmunology & Neuroinflammation, Bd. 8, Nr. 5, e1027

Abstract

Objective To analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases. Methods Retrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating disease, and healthy controls with MOG alpha-1-IgG positive (n = 202) or negative serostatus (n = 176). Samples were analyzed for their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG Ig domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from multiple species using live cell-based, tissue immunofluorescence assays and ELISA. Results The strongest IgG reactivities were directed against the longest MOG isoforms alpha-1 (the currently used standard test for MOG-IgG) and beta-1, whereas the other isoforms were less frequently recognized. Using principal component analysis, we identified 3 different binding patterns associated with non-MS disease: (1) isolated reactivity to MOG-alpha-1/beta-1 (n = 73), (2) binding to MOG-alpha-1/beta-1 and at least one other alpha, but no beta isoform (n = 64), and (3) reactivity to all 6 MOG isoforms (n = 65). The remaining samples were negative (n = 176) for MOG-IgG. These MOG isoform binding patterns were associated with a non-MS demyelinating disease, but there were no differences in clinical phenotypes or disease course. The 3 MOG isoform patterns had distinct immunologic characteristics such as differential binding to soluble MOG-ecIgD, sensitivity to MOG mutations, and binding to human MOG in ELISA. Conclusions The novel finding of differential MOG isoform binding patterns could inform future studies on the refinement of MOG-IgG assays and the pathophysiologic role of MOG-IgG.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2332-7812
• Sprache: Englisch