Study Finds Higher B-Cell Levels in African American Patients with Multiple Sclerosis

According to the National Multiple Sclerosis Society, the prevalence of multiple sclerosis (MS) is higher in white individuals than in African Americans (4 out of 1,000 people versus 3 out of 1,000 people). However, Black people with MS experience faster disability progression and more brain atrophy than their white counterparts.

It is believed that reasons for these racial disparities may include socioeconomic factors, but the true causes are not fully understood. Some researchers believe that immunologic differences may also play a role.

Researchers at the New York University Grossman School of Medicine conducted a retrospective study to compare the immune cell counts in the cerebral spinal fluid (CSF) of white and African American individuals with MS. The study results were published earlier this month in Multiple Sclerosis and Related Disorders.

The study, led by Haotian Xue, M.D., included 76 patients with MS who had been treated at the NYU Multiple Sclerosis Comprehensive Care Center between 2011 and 2021. Of all the participants, 56 self-identified as white, and 20 as African American. The average age of onset of MS was 36 years and 38 years for African American and white individuals, respectively. The average age at CSF collection was 39 years in African Americans and 41 years in whites.

Results showed that African American and white participants had similar levels of many immune cell types, such as natural killer cells, monocytes, and T-cells. However, compared with white participants, African American patients had significantly higher levels of B-lineage cells, specifically those expressing the inflammatory protein markers CD19 and CD20. When looking at CD19-expressing cells, the concentration in the CSF of African Americans was 5.46% versus 2.26% for white participants. The concentration of CD20-expressing cells was 4.64% for African Americans and 1.91% for white patients.

B-cells play a significant role in antibody production, including immunoglobulin G (IgG), which was also found at increased levels in the African American group. B-cell overexpression is also a risk factor for accelerated disability in MS.

The researchers wrote, “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 authors suggest that up-and-coming Bruton’s tyrosine kinase (BTK) inhibitors, currently in late-stage clinical development as potential oral treatments for MS, may be of particular benefit for African Americans with MS. These include Roche’s fenebrutinib, Merck’s evobrutinib, and Sanofi’s tolebrutinib. All candidates are designed to cross the blood-brain barrier and block B-cell activation.

“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 CNS 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 authors concluded.