{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:26:53Z","timestamp":1786984013701,"version":"build-2736575974"},"reference-count":43,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"abstract":"\n Importance<\/jats:title>\n Disorders affecting the spinal cord (myelopathies) can cause severe disability. Despite diagnostic advances, approximately 12% to 18% of myelopathy cases continue to elude an etiological diagnosis, hampering effective treatment.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To describe a novel autoantibody associated with idiopathic myelopathy (IM) and report its clinical, radiographic, and metabolic characteristics.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective case-control study was conducted from May 2014 to October 2025 at 4 tertiary care centers. Biofluids from 148 patients diagnosed with IM were evaluated based on clinical evidence of myelopathy without an identified etiology. Biofluids from patients with other neurological diseases (ONDs; n\u2009=\u200932) or known autoimmune myelitis (n\u2009=\u200930) were used for comparison. Proteomewide phage display was used to discover novel autoantibodies. Targeted immunoassays were used to screen for a candidate autoantibody. Downstream metabolites were measured in the cerebrospinal fluid (CSF).<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Autoantibody status.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Prevalence, clinical phenotype, CSF profile, and magnetic resonance imaging pattern of autoantibody-positive IM.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Autoantibodies targeting the transcobalamin receptor (CD320) responsible for cellular transport of vitamin B\n 12<\/jats:sub>\n were identified in 18 of 32 individuals with IM (56%) in a discovery cohort (mean [SD] age, 54 [14] years; 19 male). Bioactive vitamin B\n 12<\/jats:sub>\n concentration was decreased in the CSF of individuals with positive anti-CD320 test results compared with that of control individuals with ONDs (mean [SD], 15.1 [2.3] pmol\/L vs 22.9 [10.7] pmol\/L;\n P<\/jats:italic>\n \u2009=\u2009.03), indicative of autoimmune vitamin B\n 12<\/jats:sub>\n central deficiency. Compared to individuals with IM and negative anti-CD320 test results, those with IM and positive anti-CD320 test results demonstrated a higher frequency of subacute time course (n\u2009=\u200910 [56%] vs n\u2009=\u20091 [7%];\n P<\/jats:italic>\n \u2009=\u2009.008), normal CSF profile (n\u2009=\u200915 [83%] vs n\u2009=\u20097 [50%];\n P<\/jats:italic>\n \u2009=\u2009.04), and dorsolateral spinal cord abnormalities on magnetic resonance imaging (n\u2009=\u200911 [61%] vs n\u2009=\u20091 [7%];\n P<\/jats:italic>\n \u2009=\u2009.003). In 2 independent validation cohorts comprising 91 and 25 patients with IM, anti-CD320 was detected in 41 (45%) and 12 (48%) patients, respectively. Comorbid anti-CD320 antibodies were detected in a smaller proportion of patients with other known autoimmune etiologies of myelopathy. Five individuals with IM and positive anti-CD320 test results received vitamin B\n 12<\/jats:sub>\n supplementation with or without concurrent immunosuppression, and 4 of 5 showed clinical improvement.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this study, autoimmune vitamin B\n 12<\/jats:sub>\n central deficiency was associated with IM. Screening for anti-CD320 antibodies followed by metabolic confirmation of a CNS-restricted vitamin B\n 12<\/jats:sub>\n deficiency may be considered in the diagnostic evaluation of myelopathy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.2778","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:30:23Z","timestamp":1786980623000},"source":"Crossref","is-referenced-by-count":0,"title":["Anti-CD320 Autoantibodies and Central Nervous System Vitamin B\n 12<\/sub>\n Deficiency in Idiopathic Myelopathy"],"prefix":"10.1001","author":[{"given":"John V.","family":"Pluvinage","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, San Francisco"},{"name":"Weill Institute for Neurosciences, University of California, San Francisco"},{"name":"Arc Institute, Palo Alto, 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