{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T11:30:45Z","timestamp":1770118245094,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,30]]},"group-title":"Neurology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Disorders affecting the spinal cord (myelopathies) can cause severe disability. Despite diagnostic advances, approximately 12-18% of myelopathy cases continue to elude an etiological diagnosis, hampering effective treatment.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This retrospective, multicenter, tertiary care cohort study conducted from 2014 to 2025 evaluated archived biofluids from patients with IM, known autoimmune myelitis, or other neurological diseases (ONDs). Proteome-wide 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                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Autoantibodies targeting the transcobalamin receptor (CD320) responsible for cellular transport of vitamin B12 were identified in 18 out of 32 IM patients (56%) in a discovery cohort. Bioactive B12 concentration was decreased in the CSF of anti-CD320 positive patients compared to OND controls (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0273), indicative of autoimmune B12 central deficiency (ABCD). Compared to anti-CD320 negative IM cases, anti-CD320 positive IM cases demonstrated a higher frequency of subacute time course (56% vs 7%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.008), normal CSF profile (83% vs 50%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.044), and dorsolateral spinal cord abnormalities on magnetic resonance imaging (MRI) (61% vs 7%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003). In two independent validation cohorts comprising 94 and 25 patients with IM, anti-CD320 was detected in 43 (46%) and 12 (48%) patients, respectively. Comorbid anti-CD320 was detected in a smaller proportion of patients with other known autoimmune etiologies of myelopathy. Five anti-CD320 positive IM patients received B12 supplementation with or without concurrent immunosuppression, and four out of five clinically improved.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ABCD is associated with a substantial proportion of IM. Screening for anti-CD320 followed by metabolic confirmation of a CNS-restricted B12 deficiency may be considered in the diagnostic evaluation of myelopathy.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.29.26345179","type":"posted-content","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:00:55Z","timestamp":1769814055000},"source":"Crossref","is-referenced-by-count":0,"title":["Anti-CD320 Autoantibodies and Central Nervous System Vitamin B12 Deficiency in Idiopathic Myelopathy"],"prefix":"10.64898","author":[{"given":"John V.","family":"Pluvinage","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA"},{"name":"Weill Institute for Neurosciences, UCSF, San Francisco, CA, USA"},{"name":"Arc Institute, Palo Alto, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Acero-Garces","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, MD, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Greco","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Unit, IRCCS Mondino Foundation, Pavia, Italy"},{"name":"Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carson E.","family":"Moseley","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA"},{"name":"Weill Institute for Neurosciences, UCSF, San Francisco, CA, 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