Anti-CD320 Autoantibodies and Central Nervous System Vitamin B12 Deficiency in Idiopathic Myelopathy.
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Pluvinage John V, Acero-Garces David, Greco Giacomo, Moseley Carson E, Sidhu Sukhman, Zorn Kelsey C, Kondapavulur Sravani, Richie Megan, Douglas Vanja, Mohan Sonam, Neely John, Masciocchi Stefano, Businaro Pietro, Sarreón Alexis García, Gifreu Ariadna, McCutcheon Krista, Caspar Colette, Zamecnik Colin, Tubati Asritha, Asencor Andoni I, Tugizova Madina, Louine Martineau, Zuroff Leah, Gerdts Josiah, Karalius Mary, Nylander Alyssa, Liu Max, Daghlas Iyas, Suleiman Leena, Nguyen Todd, Meyer Benjamin, Ibarra Karen, Chow Felicia, Galati Alexandra, Mina Yair, Toro Camilo, Kang Min, Shah Maulik, Guterman Elan L, Suen Catherine G, Guo Chu-Yueh, Bevan Carolyn, Wesley Sarah F, Kvam Kathryn, Lee Sydney, Abdelhak Ahmed, Martin Thomas, Huang Yun-Han, Berman Sarah B, Linnoila Jenny, Engstrom John, McCaddon Andrew, Green Ari J, Green Ralph, Cree Bruce, Hauser Stephen, DeRisi Joseph L, Pleasure Samuel J, Gelfand Jeffrey M, Bravo Gary Álvarez, Gastaldi Matteo, Pardo Carlos A, Wilson Michael R
Аннотация
METHODS: 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).
RESULTS: 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 ( P = 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%, P = 0.008), normal CSF profile (83% vs 50%, P = 0.044), and dorsolateral spinal cord abnormalities on magnetic resonance imaging (MRI) (61% vs 7%, P = 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.
CONCLUSIONS: 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.