The CD20 inhibitor Ocrevus (ocrelizumab) is known to quickly target and deplete B-cells in individuals with multiple sclerosis (MS). However, a new study indicates that ongoing treatment also results in noteworthy changes to immune T-cells.
After approximately six months of treatment, patients exhibited changes in T-cells, specifically an increase in regulatory T-cells, which help regulate other immune cells’ activities. These effects weren’t as pronounced at earlier stages of treatment.
The scientists behind the study mentioned, “Understanding this sequential pattern may be critical to optimizing the timing and duration of anti-CD20 therapy in MS.”
The research titled “First the B cells fall, then the T cells follow: temporal immunological shift with ocrelizumab in multiple sclerosis” appeared in the Journal of Neurology.
Ocrevus affects a key protein on B-cells
In MS, the immune system mistakenly attacks healthy brain and spinal cord tissue. Various immune cells are involved in these attacks, but B-cells and T-cells are particularly crucial.
Ocrevus is used for treating adults with both relapsing and primary progressive forms of MS. Administered through an infusion, it effectively reduces disease activity and slows down the progression of disability.
This medication’s active component is an antibody targeting the CD20 protein found on mature B-cells, resulting in their depletion. Research indicates that this depletion may also lead to changes in the behavior of other immune cells.
To delve deeper, researchers in Italy examined the long-term effects of Ocrevus on the immune systems of 15 MS patients. They analyzed publicly available gene expression data from these patients’ immune cells, collecting samples before treatment, after two weeks, and at the six-month mark.
Therapy appears to modify regulatory T-cells
During their examination of the two-week samples, the researchers identified notable differences among various B-cell subtypes and a consistent decline in B-cell gene activity. Concurrently, there was an uptick in anti-inflammatory molecules and an increase in the activity of genes that help monocytes reach inflammatory sites. This may serve as a compensatory mechanism for the loss of B-cells.
However, there weren’t any significant alterations in T-cell levels or other immune cells at this early stage.
By the six-month mark, significant changes were observed in T-cell pathways that had not been evident at two weeks. For example, there was a notable decrease in inflammatory molecule production and reduced activation of CD4-positive T-cells, which play a key role in regulating immune responses.
Our data indicate that anti‑CD20 treatment leads to swift B-cell depletion, whereas alterations in T cell-related pathways emerge more gradually and become most noticeable by 6 months.
Additionally, the six-month treatment appeared to enhance the activity and resilience of regulatory T-cells, potentially supporting long-term immunomodulatory effects in MS. The researchers noted that this might mark a delayed biological effect crucial for Ocrevus’s long-lasting effectiveness.
Moreover, the suppression of B-cell functions continued at the six-month point and sometimes became more pronounced. The scientists concluded that while anti-CD20 treatment rapidly depletes B-cells, alterations in T-cell pathways appear more slowly, becoming clearer at the six-month stage. They emphasized the need for further research at intermediate timepoints to better understand these gene activity changes and their potential as indicators of long-term treatment success.
