Investigating oligodendrocyte myelin glycoprotein as a novel autoantibody candidate in demyelinating disorders

Over the past decade, increasing studies of autoantibodies associated with inflammatory disorders of the central nervous system (CNS) have further expanded the spectrum of demyelinating diseases. The discovery of anti-AQP4 and anti-MOG antibodies has remarkably enabled differential diagnostic criteria formation for patients with Neuromyelitis Optica Spectrum Diseases and MOG-related Antibody Disease. Despite this, most patients in that spectrum are still either undiagnosed or misdiagnosed due to their atypical features, and the actual target of autoimmune responses is unknown. Associating relevant patients with novel autoantibodies to be discovered is crucial, particularly in the proper treatment decisions and showing improvement. Oligodendrocyte myelin glycoprotein (OMGp) is a promising autoantibody candidate because it is a glycoprotein explicitly expressed on the surfaces of CNS neurons and oligodendrocytes. In this study, the "live cell-based assay," a "gold standard" for numerous autoantibody detections, was first optimized and developed to detect anti-OMGp antibodies. Subsequently, the serum of 800 people, aged between 8 and 90, with a gender distribution of female: male with a 1.84 ratio were screened for anti-OMGp antibody positivity employing this test. The CSF of 86 patients out of these 800 people was also scanned using the same method. The cut-off value was determined using 30 healthy controls. While net positivity was detected in seventeen sera, all CSF samples were negative. All patients with positive anti-OMGp antibodies had negative anti-MOG and anti-AQP4 antibodies. The average age of positive cases is 46 (range 23-63), female-male ratio is 2.4. Atypical demyelinating traits were present in all positive patients except one. Some of those features were as follows: tumefactive lesion in five patients, brainstem lesions in eight patients, diffuse ADEM-like lesions in three patients, long segment transverse myelitis in two patients, and cortical lesion in three patients. Furthermore, in most positive cases, steroid response was limited during attacks, and treatments such as PLEX and IVIg were required. Thus, this study tested anti-OMGp antibodies in an atypical feature-rich demyelinating disease cohort for the first time in the literature; seventeen positive patients were identified. Atypical demyelinating disease features were detected in positive patients regarding clinical, radiological, and treatment response. Our findings indicate that anti-OMGp antibodies may cause a distinct disease entity and should be tested, especially in individuals with atypical demyelinating disease characteristics.