Can autoantibodies and vitamin B12 deficiency in the brain indicate autoimmune neuropsychiatric symptoms?

While studying a 67-year-old woman with symptoms of unsteadiness (ataxia), tremors, and difficulty speaking, researchers identified an autoantibody that causes B12 deficiency in the brain and results in neurological symptoms. To their surprise, researchers discovered that this autoantibody was also found in other autoimmune disease patients and was approximately four times as prevalent in patients with neuropsychiatric systemic lupus erythematosus (SLE) than in those with non-neurological SLE.

The discovery began when the 67-year-old patient enrolled in a study focused on identifying novel autoantibodies in suspected neuroinflammatory disease, using a screening technology called phage immunoprecipitation sequencing. Researchers found that the patient had autoantibodies in her brain that target a receptor—CD320—which is important in B12 intake. This meant that the B12 in her cerebrospinal fluid (CSF) was "nearly undetectable" even though her regular blood tests had shown normal results. The patient's symptoms improved once she was treated with immunosuppressants and high-dose B12 supplementation.

Researchers began to test other individuals enrolled in the same study and found seven participants with anti-CD320 autoantibodies, four of whom also had a B12 deficiency in the CSF. In a group of patients with multiple sclerosis, the presence of the antibody was also highly predictive of high levels of CSF methylmalonic acid, a metabolic marker of B12 deficiency. Researchers are still investigating the relevance of anti-CD320 in healthy controls, and have hypothesized that some individuals with anti-CD320 may develop symptoms later in life.

This autoantibody was also found to be four times as prevalent in SLE patients with neurological symptoms than those without. The evidence suggests that the autoantibody impairs the transport of B12 across the blood-brain barrier, leading to B12 deficiency in the brain and affecting the central nervous system. This could be a significant step in understanding neurological symptoms, which are common among autoimmune disease patients.

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