African American MS patients have high B-cell levels in CSF, study says

People with multiple sclerosis (MS) of African descent had higher levels of inflammatory B-cells in the fluid around the brain and spinal cord compared with white MS patients in a small U.S. study.

These findings may help to explain why Black people with MS tend to experience a faster worsening of disability. They also imply that Black MS patients may especially benefit from disease treatments that reduce the activity of B-cells in the brain, particularly a group now in clinical testing, its researchers said.

The study, “African American patients with Multiple Sclerosis (MS) have higher proportions of CR19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients,” was published in Multiple Sclerosis and Related Disorders.

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A neurological disorder, MS is caused by the immune system launching an inflammatory attack that damages healthy parts of the brain and spinal cord.

Race-based disparities in health outcomes for people with MS are well documented. Compared to their white peers, Black people with MS tend to experience faster disability progression and more brain atrophy.

Reasons for these racial disparities aren’t fully understood. Socioeconomic factors likely play a notable role, but differences in immune activity also may contribute.

Researchers largely at New York University’s medical school analyzed immune cell counts in cerebrospinal fluid (CSF) — the liquid that surrounds the brain and spinal cord — collected from 74 people with MS, all being treated at that university’s MS center between 2011 and 2021.

Among the patients, 54 identified as white and 20 as African American; roughly three-quarters of patients were female. The average age at MS onset was in the late 30s in both racial groups, and average age at CSF collection was around 40 in both groups.

Total levels of immune cells were comparable between African American and white patients. Levels of many specific immune cell types, including T-cells and natural killer cells, also were not significantly different.

Significantly higher B-cell counts seen around the brain and spinal cord

But results showed that African American patients had significantly higher counts of B-cells, specifically higher numbers of B-cells carrying the inflammatory protein markers CD19 (5.46% vs. 2.26%) or CD20 (4.64% vs. 1.91%).

“Our finding on the overrepresentation of CD19+ and CD20+ B-lineage cells in the CSF of MS patients with African ancestry adds to the body of evidence that the immune system of MS patients in this population is relatively more polarized toward B-cell responses compared to [white] patients,” the researchers wrote.

B-cells are the immune cells responsible for making antibodies, and results also showed that African American patients had a higher average IgG index, which is indicative of higher antibody levels in the CSF. IgG, or immunoglobulin G, is a common type of antibody.

“The relative overrepresentation of B-cells in CSF and higher [IgG] index in [African American patients] may correlate to the more severe disease course in this population as patients with a higher IgG index in CSF and relative B-cell predominance in CSF have been shown to have faster disease progression,” the researchers wrote.

These findings imply that treatments designed to lower B-cell activity in the brain might be of particular value for Black MS patients, they added.

In particular, the researchers said these data support the potential of oral Bruton’s tyrosine kinase (BTK) inhibitors currently in clinical development — such as fenebrutinib, evobrutinib, and tolebrutinib — which are designed to enter the brain and reduce B-cell activation.

Several approved MS treatments also work to deplete B-cells by targeting the CD20 protein, but these therapies have little ability to enter the brain.

“Our observation of higher proportions of CD19+/CD20+ cells in the CSF of [African American] patients with MS suggests that agents that may deplete or down-regulate B-cell activity in the [central nervous system] compartment, e.g., some Bruton’s tyrosine kinase (BTK) inhibitors, which are now in advanced stages of development, may be especially efficacious in this population,” the scientists concluded.