Research

The article by Pluvinage et al (published in Sci. Transl. Med. 2024; 16:eadl3758) explores a novel autoimmune cause of vitamin B12 deficiency in the central nervous system (CNS), termed "Autoimmune B12 Central Deficiency" (ABCD). Researchers from San Francisco discovered autoantibodies targeting the transcobalamin receptor (CD320), a key protein in vitamin B12 transport, impairing B12 uptake into the brain despite normal serum B12 levels.
The authors have used phage display technology, and demonstrated the presence of a specific autoantibody against the CD320 receptor in a patient with poorly understood progressive neurological symptoms (e.g., tremor, ataxia, speech issues). It was observed that the autoantibody blocks B12 uptake into the brain, causing B12 deficiency in nervous tissue and leading to a variety of neurological symptoms. 
CD320 antibodies were also found in other patients with unexplained neurological deficits, neuropsychiatric lupus (21.4% prevalence), and some healthy controls (6% prevalence).
A genome-wide CRISPR screen revealed that an alternate pathway via LDL receptors compensates for CD320 loss in hematopoietic cells but not in the CNS, explaining the tissue-specific effects.
In the index patient, high-dose systemic vitamin B12 supplementation and immunosuppressive therapy showed improvements in CSF B12 levels and clinical symptoms. Larger studies are needed to explore the prevalence and long-term effects of these autoantibodies in people with symptoms suggestive of B12 deficiency, and the therapeutic role of B12 in neuropsychiatric disorders.