Eva-Maria Wendel

Background/Purpose: Optic neuritis (ON) is a rare disease that may remain a single episode or transform into MS. OCBs and spinal MRI lesions have already been identified as prognostic factors. Aim: Our aim was to evaluate if the presence of more than one elevated antibody index of measles, rubella, and/or varicella-zoster (MRZ) is an indicator of risk of conversion. Methods: In total, 228 patients diagnosed with ON between 1990 and 2013 were included in this retrospective study. All children had a data set consisting of age, sex, ON type, MRI, and detailed CSF studies, including the presence of OCBs and MRZ reactions and a follow-up of at least 1.5 years. Children were then divided into two groups: those who developed MS according to the McDonald criteria 2010 (n = 92) and those who did not (n = 136). Binary logistic regression analysis was used to assess the relationship between the different prognostic factors and conversion to MS. Positive (PPV) and negative predictive values were calculated. Results: Binary logistic regression analysis revealed that an MS-like MRI (p < 0.001), positive OCBs (p = 0.002), and a positive MRZ reaction (p < 0.001) were significant prognostic factors for conversion to MS after ON. Calculated PPVs showed a positive MRZ reaction alone to already be a good predictor (PPV 0.90 (95%CI: 0.82 to 0.95), p < 0.001). The best prediction was possible with a combination of cMRI, the presence of OCBs, and a positive MRZ reaction (PPV 1.00 (0.93 to 1.00), p < 0.001). Conclusions: Our findings show that a positive MRZ reaction alone already has a high predictive value for future conversion to MS and should be included in the workup of a child with an initial demyelinating event.

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.