Prevalence of anti-myelin oligodendrocyte glycoprotein antibodies across neuroinflammatory and neurodegenerative diseases

• Published in: Journal of the neurological sciences Vol. 461; p. 123041
• Main Authors: Trivedi, Ritu R., Archambault, Angela S., Pavlak, Clarice, Gastaldi, Matteo, Cantoni, Claudia, Ghezzi, Laura, Cross, Anne H., Miller, Timothy M., Wu, Gregory F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2024
• Subjects: Adult; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - immunology; Animals; Autoantibodies - blood; Autoantibody; Cell based assay; Female; Humans; Immunoglobulin G - blood; Male; Middle Aged; MOG; MOGAD; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Myelin-Oligodendrocyte Glycoprotein - immunology; Neurodegeneration; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - diagnosis; Neurodegenerative Diseases - immunology; Neuroinflammatory Diseases - blood; Neuroinflammatory Diseases - immunology; Neurology; MS53; CBA; MOG; Autoantibody; ALS; Amyotrophic lateral sclerosis; CNS; MOGAD; AQP4; ATCC; HAND; OCB; NMO; MFI; EV; Neurodegeneration; ADEM; CSF; Cell based assay; NEALS; HC; Ig; ELISA; Healthy control; Multiple sclerosis; Neuromyelitis optica spectrum disorder; Central nervous system; Immunoglobulin; Cerebrospinal fluid; mean fluorescent intensity; Myelin oligodendrocyte glycoprotein; American Type Culture Collection; Cell-based assay; MOG antibody-associated disease; Northeast ALS Consortium; Oligoclonal bands; Human immunodeficiency virus-1 associated neurocognitive disorder; Aquaporin-4; Acute disseminated encephalomyelitis; enzyme-linked immunosorbent assay; extracellular vesicle
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2024.123041

Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in patients with CNS diseases, including MS and ALS. In total, 771 serum samples from the John L. Trotter MS Center and the Northeast ALS Consortium were examined using a live cell-based assay for detection of anti-MOG IgG1. Samples from three cohorts were tested in blinded fashion: healthy control (HC) subjects, patients with clinically diagnosed MOGAD, and an experimental group of ALS and MS patients. All samples from established MOGAD cases were positive for anti-MOG antibodies, while all HC samples were negative. Anti-MOG IgG1 was detected in 65 of 658 samples (9.9%) from MS subjects and 4 of 108 (3.7%) samples from ALS subjects. The presence of serum anti-MOG IgG1 in MS and ALS patients raises questions about the contribution of these antibodies to disease pathophysiology as well as accuracy of diagnostic approaches for CNS inflammatory diseases. •Anti-MOG IgG1 was detected in 9.9% of subjects with multiple sclerosis•Anti-MOG antibody levels tended to decline over time yet persist over many years in patients who do not have MOGAD•3.7% of subjects with amyotrophic lateral sclerosis harbored serum anti-MOG antibodies