دورية أكاديمية
Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.
| العنوان: | Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. |
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| المؤلفون: | Pluvinage JV; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Ngo T; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Fouassier C; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., McDonagh M; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Holmes BB; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Bartley CM; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA.; Department of Psychiatry and Behavioral Sciences, UCSF, San Francisco, CA 94158, USA., Kondapavulur S; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA.; Department of Neurological Surgery, UCSF, San Francisco, CA 94158, USA., Hurabielle C; Department of Medicine, Division of Rheumatology, UCSF, San Francisco, CA, 94158, USA., Bodansky A; Department of Pediatrics, Division of Critical Care, UCSF, San Francisco, CA 94158, USA., Pai V; Bruker Cellular Analysis, Emeryville, CA, 94608, USA., Hinman S; Bruker Cellular Analysis, Emeryville, CA, 94608, USA., Aslanpour A; Bruker Cellular Analysis, Emeryville, CA, 94608, USA., Alvarenga BD; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Zorn KC; Department of Biochemistry and Biophysics, UCSF, San Francisco, CA 94158, USA., Zamecnik C; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., McCann A; Bevital, Bergen 5068, Norway., Asencor AI; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Huynh T; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Browne W; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Tubati A; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Haney MS; Department of Neurology, Stanford University, Stanford, CA 94304, USA., Douglas VC; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Louine M; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Cree BAC; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Hauser SL; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Seeley W; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Baranzini SE; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Wells JA; Department of Pharmaceutical Chemistry, UCSF, San Francisco, CA 94158, USA., Spudich S; Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA., Farhadian S; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA., Ramachandran PS; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Gillum L; Bass Medical Group, Pleasant Hill, CA 94523, USA., Hales CM; Department of Neurology, Emory University, Atlanta, GA 30322, USA., Zikherman J; Department of Medicine, Division of Rheumatology, UCSF, San Francisco, CA, 94158, USA., Anderson MS; Diabetes Center, UCSF, San Francisco, CA 94143, USA.; Department of Medicine, Division of Endocrinology, UCSF, San Francisco, CA 94158, USA., Yazdany J; Department of Neurological Surgery, UCSF, San Francisco, CA 94158, USA., Smith B; Division of Neuroimmunology and Neurovirology, National Institute of Neurologic Disorders and Stroke, Bethesda, MD 20824, USA., Nath A; Division of Neuroimmunology and Neurovirology, National Institute of Neurologic Disorders and Stroke, Bethesda, MD 20824, USA., Suh G; Department of Medicine, Division of Infectious Disease, Mayo Clinic, Rochester, MN 55905, USA., Flanagan EP; Department of Neurology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA., Green AJ; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Green R; Department of Pathology and Laboratory Medicine, University of California, Davis, CA 95616, USA., Gelfand JM; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., DeRisi JL; Bruker Cellular Analysis, Emeryville, CA, 94608, USA.; Chan Zuckerberg Biohub San Francisco, San Francisco, CA 94158, USA., Pleasure SJ; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Wilson MR; Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA. |
| المصدر: | Science translational medicine [Sci Transl Med] 2024 Jun 26; Vol. 16 (753), pp. eadl3758. Date of Electronic Publication: 2024 Jun 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Vitamin B 12 Deficiency*/immunology , Vitamin B 12*/blood , Autoantibodies*/blood , Autoantibodies*/immunology, Humans ; Female ; Receptors, Cell Surface/metabolism ; Antigens, CD/metabolism ; Middle Aged ; Autoimmune Diseases/immunology ; Autoimmune Diseases/blood ; Blood-Brain Barrier/metabolism ; Male |
| مستخلص: | 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. |
| المشرفين على المادة: | P6YC3EG204 (Vitamin B 12) 0 (Autoantibodies) 0 (transcobalamin receptor) 0 (Receptors, Cell Surface) 0 (Antigens, CD) 0 (CD320 protein, human) |
| تواريخ الأحداث: | Date Created: 20240626 Date Completed: 20240626 Latest Revision: 20240704 |
| رمز التحديث: | 20240704 |
| DOI: | 10.1126/scitranslmed.adl3758 |
| PMID: | 38924428 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1946-6242 |
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| DOI: | 10.1126/scitranslmed.adl3758 |