Differential binding of serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG) in inflammatory demyelinating diseases is associated with clear structural differences and may represent different antibody clones, according to study results published in Neurology.
Previous studies have shown an association between antibodies against MOG and various neurological disorders. While most studies have used the MOGα1 isoform for the measurement of MOG-IgG, there are additional MOG isoforms with differences in the composition of the intracellular C terminus resulting in alpha or beta isoforms.
The objective of the current study was to investigate the serum IgG antibody response to different MOG isoforms and to determine the added value of using additional MOG isoforms on MOG-IgG in cell based assays.
The retrospective case-control study included serum samples from 378 patients with inflammatory demyelinating diseases, including 214 patients with aquaporin-4– seronegative non-MS demyelinating disease (typically associated with MOG-IgG), 64 patients with MS, and 100 healthy controls. All serum samples were analyzed to determine MOG-IgG serostatus using MOGα1 live cell based assay (176 negative and 202 positive).
Study researchers also assessed serum samples to determine their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG immunoglobulin domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from several species using live cell-based, tissue immunofluorescence assays and ELISA.
The strongest antibody reactivities were directed against the longest MOG isoform α1 (median titer 1:160; 25th-75th percentile; 0-640) and β1 (median titer 1:160; 0-640), while the other isoforms were less frequently identified.
There were several binding patterns that were predominantly associated with demyelinating diseases other than multiple sclerosis: (1) equal binding to α1 and β1 and no binding to the other isoforms (pattern α1β1, 73 cases), (2) equal binding to α1 and β1, weaker binding to α2 and α3, and no binding to the other isoforms (pattern α1-3β1, 64 cases), (3) binding to all 6 MOG isoforms (pattern α1-3β1-3, 65 cases).
While these binding patterns were associated with demyelinating diseases other than multiple sclerosis, there was no association with clinical presentation, disease course, or neuropathology.
Study researchers completed additional immunologic investigations, showing that MOG-IgG of the α1-3β1-3 binding pattern also bound to soluble MOG-ecIgD with high affinity.
The study had several limitations, including the retrospective design, the heterogeneous observation period, and missing data on treatment.
“[O]ur novel finding of differential MOG isoform binding patterns could explain previous discrepant reports and instruct future studies to improve and refine MOG-IgG antibody assays,” concluded the study researchers.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Schanda K, Peschl P, Lerch M, et al. Differential binding of autoantibodies to MOG isoforms in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm. Published online June 15, 2021. doi:10.1212/NXI.0000000000001027