A NOVEL autoantibody targeting the vitamin B12 transport receptor CD320 has been identified in patients with idiopathic myelopathy, linking autoimmune vitamin B12 deficiency to previously unexplained spinal cord disease.
Myelopathies have remained a significant cause of disability, yet up to 18% of cases continue to elude an etiological diagnosis. This gap has hampered effective treatment, particularly when serum vitamin B12 appears normal but a central nervous system restricted deficiency goes undetected. Researchers have therefore sought biomarkers for an idiopathic myelopathy subgroup driven by autoimmune disruption of vitamin B12 transport.
The retrospective case-control study ran from May 2014 to October 2025 across four tertiary care centres. Biofluids from 148 patients with idiopathic myelopathy were analysed, with 32 patients with other neurological diseases and 30 with autoimmune myelitis as comparators. A discovery cohort of 32 patients (mean age 54 years, SD 14; 19 male) underwent phage display to identify candidate autoantibodies, followed by immunoassays and CSF vitamin B12 measurement. Two validation cohorts of 91 and 25 patients were then tested.
Anti-CD320 autoantibodies were detected in 18 of 32 individuals (56%) in the discovery cohort. CSF bioactive vitamin B12 was lower in antibody positive individuals than in controls with other neurological diseases (mean 15.1 pmol/L, SD 2.3, vs 22.9 pmol/L, SD 10.7; P=.03). Antibody positive patients more frequently showed a subacute time course (56% vs 7%; P=.008), a normal CSF profile (83% vs 50%; P=.04), and dorsolateral cord abnormalities on MRI (61% vs 7%; P=.003). Anti-CD320 was detected in 45% and 48% of patients across the validation cohorts, and less often in known anti-AQP4 or anti-MOG myelitis. Four of five antibody positive patients given B12 supplementation improved clinically.
These findings have established a novel association between anti-CD320 autoantibodies, central nervous system restricted vitamin B12 deficiency, and idiopathic myelopathy, a condition that has remained diagnostically elusive.
Screening for anti-CD320, followed by metabolic confirmation of CSF B12 deficiency, may warrant consideration in myelopathy evaluation. As this remains observational, the findings demonstrate association rather than causation, and larger trials are needed to confirm whether B12 supplementation improves outcomes.
Reference
Pluvinage JV et al. Anti-CD320 autoantibodies and central nervous system vitamin B12 deficiency in idiopathic myelopathy. JAMA Neurol. 2026;DOI:10.1001/jamaneurol.2026.2778.
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