A groundbreaking study from the University of California, San Francisco (UCSF) has identified a novel autoimmune disorder that prevents vitamin B12 from reaching the brain. This discovery offers a potential explanation for previously unexplained neurological symptoms, such as tremors and speech difficulties, experienced by some individuals. While the findings are promising, further research is needed to understand the prevalence and full impact of this condition.
This breakthrough emerged from a UCSF project dedicated to unraveling complex neurological mysteries potentially linked to undiscovered immune system malfunctions. “Our aim was to leverage advanced diagnostic tools, some of which are solely for research, to decipher the mechanisms behind these diseases and propel the field forward,” explained Dr. John Pluvinage, a neurology resident at UCSF’s School of Medicine.
Unraveling the Mystery: A Case Study
The initial case involved a 67-year-old woman who began experiencing neurological problems in 2014. Standard tests, including those for autoantibodies targeting the nervous system, failed to identify the cause. Eventually diagnosed with lupus, she gradually improved with treatment over the next three years. However, by 2021, she developed speech difficulties and cognitive decline. Despite normal blood B12 levels, no reversible causes of dementia were found. Vitamin B12 is crucial for brain health, and its deficiency can lead to various neurological issues.
The woman enrolled in the UCSF study, which employed phage display, a cutting-edge method, to detect harmful autoantibodies in the brain. This technique involves using phages (viruses that infect bacteria) to display a wide array of human proteins on their surface. When exposed to the patient’s cerebrospinal fluid, antibodies bound to phages displaying specific proteins, revealing a potential autoimmune reaction. Further analysis identified the CD320 protein as the target of the patient’s antibodies.
CD320 facilitates vitamin B12 uptake by cells, particularly those near the blood-brain barrier, which regulates substances entering the brain. The researchers hypothesized that the woman’s anti-CD320 antibodies were blocking vitamin B12 from reaching her brain via the bloodstream. They also found evidence that cells outside the brain can absorb B12 through alternative pathways, explaining the patient’s normal blood B12 levels. “While her blood B12 was normal, it was almost undetectable in her cerebrospinal fluid,” Dr. Pluvinage stated. “In vitro experiments showed that her antibodies impaired B12’s ability to cross the blood-brain barrier.”
Subsequently, the team screened other study participants with unexplained neurological issues and identified seven potential cases with these antibodies. They also detected the antibodies in 20% of patients with neuropsychiatric lupus and 6% of healthy individuals without neurological problems.
Further Research and Implications
The findings, published in Science Translational Medicine, represent the initial phase of this research. Many questions remain. Not all individuals with the antibodies exhibited B12 deficiency in the brain, and healthy controls with the antibodies showed no neurological symptoms. It’s possible that some individuals with anti-CD320 antibodies may eventually develop similar neurological problems, while others might remain unaffected. The antibodies might only cause issues in individuals already predisposed to other illnesses.
“We aim to investigate these antibodies in other neurological diseases and assess their influence on disease progression,” Dr. Pluvinage explained. “We also want to understand the mystery of healthy controls with these antibodies.” He emphasized that while this discovery might explain some unexplained brain diseases, it’s not a universal solution.
The research has already benefited the initial patient. Her immunosuppressive treatment stabilized her symptoms, enabling her to play the piano again. Following the discovery, she received high-dose B12 supplements, leading to increased brain B12 levels and reported improvements in mood and cognitive function.
The researchers’ discovery offers hope for individuals with unexplained neurological symptoms and highlights the importance of continued research in this area. Further investigation will be crucial to understand the full implications of this autoimmune disorder and develop targeted therapies.
