Newly Discovered Autoimmune Disorder Saps Vitamin B From Your Brain

Scientists from the University of California, San Francisco are claiming to have discovered a novel autoimmune disorder that keeps precious vitamin B12 from reaching our brains. The condition seems to explain some people’s previously mysterious neurological symptoms, such as tremors and difficulty speaking. There are still many unanswered questions surrounding the disorder, including how commonly it actually sickens people.

The team’s discovery was made through an ongoing project at UCSF intended to solve tough medical mysteries involving the brain that might be connected to unknown flaws within a person’s immune system.

“The goal of the study was: Can we use advanced diagnostics, some of which have research only-purposes, to try to figure out the mechanism of these diseases and potentially move the field forward?” project researcher John Pluvinage, a resident in neurology at UCSF’s School of Medicine, told Gizmodo over the phone.

A medical mystery solved

The patient who started this particular journey was a 67-year-old woman who first experienced neurological problems in 2014. Standard testing failed to find any clear explanation for what was happening to her, which included a search for autoantibodies that attack the body’s nervous system. 

She was eventually diagnosed with and treated for the autoimmune disease lupus, and over the next three years she slowly improved. By 2021, however, she began to have trouble finding her words, while exhibiting other signs of cognitive decline. A new round of tests failed to identify any known but reversible causes of dementia, including blood tests measuring her levels of B12. B12 is generally important to our brain health, and not having enough of it over time can cause a wide range of neurological problems.

The woman was enrolled into the team’s study, which used a less conventional testing method to hunt for potential autoantibodies harming the brain, known as phage display. The USCF team used phages (bacteria-killing viruses) to display a vast number of proteins produced by the human body on the phages’ surface. The phages were then exposed to the patient’s cerebrospinal fluid. As they hoped, some antibodies bonded to phages displaying certain proteins, indicating a potential autoimmune response. Further study and sequencing revealed that the patient’s antibodies were attacking the CD320 protein.

CD320 helps the body’s cells take in vitamin B12 and it’s particularly common in the cells that hang around the brain-blood barrier—the membrane that selectively regulates which substances can enter and pass through the brain. Given that, the team suspected that the woman’s anti-CD320 antibodies were silently preventing the vitamin from getting to her brain through the bloodstream as usual. The team also found evidence that cells outside the brain can use a different method of taking in B12 outside of CD320, likely explaining why their patient’s blood levels of B12 still looked fine.

“What we found was that although her blood level was normal, the level of B12 in her cerebrospinal fluid was nearly undetectable. And using some in-vitro experiments, we found that the antibodies in her blood and in her cerebrospinal fluid actually impair the ability of B12 to cross the barrier,” Pluvinage said.

The team next looked for these antibodies among other patients with unexplained neurological issues enrolled in the study, finding seven potential cases. They also found the antibodies in one-fifth of a sample of patients diagnosed with neuropsychiatric lupus (lupus affecting the nervous system), and even in 6% of a small sample of healthy people with no diagnosed neurological problems.

Lingering questions

The researchers’ findings, published last month in the journal Science Translational Medicine, only represent the beginning of their detective work, and there’s still so much to learn.

For starters, while some of their other mysterious neurological cases did have these antibodies, not everyone who did had a corresponding B12 deficiency in the brain. By definition, healthy controls with these antibodies also don’t appear to have neurological issues as a result. It’s possible that some people with anti-CD320 antibodies will inevitably become sick in the same way as their original patient did over time, even if they seem fine now. But it might also be true that simply having these antibodies alone isn’t enough to cause problems. One possibility is that these antibodies can cause trouble in people who are already sick with something else—a sort of second hit to the system. 

“One area that we want to explore is looking at this antibody in other neurologic diseases, and determining whether the progression of disease is modulated by this antibody. And the second thing we want to do is explore the healthy control mystery,” Pluvinage said. He does caution that even if their discovery can explain some previously mysterious cases of brain disease, though, it won’t solve them all. “It’s tempting to think that everything could be possibly caused by this, but probably just a fraction is actually related,” he noted.

The team’s research does seem to have already helped its first patient at least. The patient’s earlier immunosuppressive treatment likely helped stabilize her symptoms, allowing her to play the piano again. And following the team’s discovery of these antibodies, the woman was given high doses of B12 supplements. Since then, her levels of B12 in the brain have risen, and she has reported improvements in her mood and cognitive function.