Unveiled Autoimmune Condition Drains Vitamin B Reserves in Your Cerebrum
Researchers from the University of California, San Francisco have allegedly uncovered a new autoimmune condition that impedes vitamin B12 from reaching our brains, a vital nutrient for brain health. This disorder might account for certain individuals' inexplicable neurological symptoms, such as shakes and speech impairments. Nonetheless, numerous questions remain unresolved about the condition, including its prevalence among people.
The team's breakthrough emerged from an on-going project at UCSF, seeking to decipher brain-related medical mysteries linked to imperfections within the immune system.
Project researcher John Pluvinage, a resident in neurology at UCSF's School of Medicine, explained their motive in a call to Gizmodo: "The aim of our study was: Could we utilize advanced diagnostics, some of which are research-exclusive, to figure out the mechanism of these diseases and potentially advance the field?"
A medical enigma tackled
The case that initiated this particular investigation was a 67-year-old woman who experienced neurological symptoms for the first time in 2014. Standard assessments failed to discover any identifiable reasons behind her condition, which included the hunt for autoantibodies targeting the nervous system.
She was ultimately diagnosed with lupus, an autoimmune disorder, and over the following three years, she saw improvements. However, in 2021, she encountered trouble articulating words and showed signs of cognitive decline. New tests proved fruitless in identifying any known causes of dementia, including B12 level checks. Lack of adequate B12 can result in a broad spectrum of neurological issues.
The woman joined the team's study, employing an unconventional approach to search for potential autoantibodies damaging the brain - phage display. Using phages, bacterium-killing viruses, the UCSF team displayed a multitude of human proteins on phage surfaces, then exposed them to the patient's cerebrospinal fluid. Antibodies linked to certain proteins were found, suggesting a possible autoimmune response. Analysis and sequencing revealed that the woman's antibodies were attacking the CD320 protein.
CD320 helps in vitamin B12 uptake and is predominant in cells adjacent to the brain-blood barrier - the selective membrane regulating which substances enter and pass through the brain. The team suspected that the woman's anti-CD320 antibodies were subtly hindering the vitamin's passage to the brain through the bloodstream. They also encountered evidence suggesting that cells outside the brain could acquire B12 through a different mechanism, explaining their patient's normal blood B12 levels.
According to Pluvinage, "We found that although her blood level was normal, the level of B12 in her cerebrospinal fluid was almost undetectable. And using in-vitro experiments, we found that the antibodies in her blood and cerebrospinal fluid actually hamper the ability of B12 to cross the barrier."
The team investigated these antibodies within other patients with unexplained neurological complications, identifying seven potential instances. They also discovered the antibodies in one-fifth of a sample from patients diagnosed with neuropsychiatric lupus (lupus impacting the nervous system), and in 6% of a small sample of healthy individuals with no recognized neurological conditions.
Unresolved queries
The researchers' findings, published in the journal Science Translational Medicine, mark the onset of their investigations. However, there remains an abundance of knowledge to acquire.
For example, while some of their other enigmatic neurological cases demonstrated these antibodies, not everyone with them experienced corresponding B12 deficiencies in the brain. Healthy controls with these antibodies also reported no neurological issues. It's possible that some individuals with anti-CD320 antibodies will eventually develop signs of neurological decline, even if they appear healthy now. Alternatively, merely having these antibodies may not be enough to cause problems. Possibly, these antibodies could cause issues in individuals who are already unwell - a secondary blow to their system.
"One area we wish to explore is investigating this antibody in other neurological diseases, and determining whether the disease's progression is influenced by this antibody. The second thing we want to investigate is the enigma surrounding healthy controls," Pluvinage noted. He emphasizes that even if their discovery can explain a portion of brain diseases, it won't solve all of them. "It's tempting to think that everything could be potentially caused by this, but likely only a fraction of it is actually related," he stated.
The team's research has already aided their first patient. The patient's initial immune-suppressive treatment likely stalled her symptoms, permitting her to play the piano again. After the team discovered these antibodies, the woman received high doses of B12 supplements. Since then, her brain B12 levels have risen, and she has reported enhancements in mood and cognitive function.
The discovers made by the UCSF team could potentially revolutionize the future of neurology, as they pave the way for the development of targeted therapies for individuals with this autoimmune condition. With advancements in science and technology, these treatments could help restore brain health and alleviate symptoms like shakes and speech impairments.
Furthermore, the understanding of this new condition could also extend beyond neurology, as similar mechanisms might be present in other autoimmune diseases. Future research in the field of health and technology could uncover new autoimmune conditions and potential treatments, ultimately improving the quality of life for many individuals.
