{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:41:10Z","timestamp":1787863270103,"version":"build-2784847793"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"753","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,6,26]]},"abstract":"<jats:p>Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.<\/jats:p>","DOI":"10.1126\/scitranslmed.adl3758","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T13:59:57Z","timestamp":1719410397000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-2783","authenticated-orcid":true,"given":"John V.","family":"Pluvinage","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA."},{"name":"Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, 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Pluvinage Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency Dryad (2024); https:\/\/doi.org\/10.5061\/dryad.6djh9w18j."}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adl3758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T14:00:03Z","timestamp":1719410403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adl3758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":50,"journal-issue":{"issue":"753","published-print":{"date-parts":[[2024,6,26]]}},"alternative-id":["10.1126\/scitranslmed.adl3758"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adl3758","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"2023-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadl3758"}}