Rituximab’s Immunosuppressive Effects Go Beyond B Cells in SSc, Study Finds

Rituximab, an immunosuppressant antibody designed to target immune B cells, has widespread effects and decreases subtypes of other immune cells called T cells in the skin and blood of people with systemic sclerosis (SSc), new research shows.

The study, titled “B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis,” was published in the journal Rheumatology International.

Rituximab is an engineered antibody developed by Roche to specifically target the cell surface protein CD20 often found in immune B-cells. It is sold under the name Rituxan in the United States, and MabThera in Europe as a treatment for certain non-Hodgkin’s lymphomas, chronic lymphocytic leukemia, and select autoimmune diseases, including SSc and multiple sclerosis.

Several studies have shown that rituximab helps patients with SSc by lessening skin scarring (fibrosis) and improving lung function. However, the mechanism by which rituximab works in SSc is still not fully understood.

Compared to healthy individuals, SSc patients present elevated levels of another type of immune cell called T cells, and of molecules produced by these cells called cytokines (immune messengers). Evidence suggests that some T-cell subtypes are particularly implicated in fibrosis development.

Now, a team of researchers in Greece studied how rituximab affects immune T cells in SSc patients.

The study included 15 SSc patients treated with rituximab, and six patients who received standard treatment. Among the rituximab group, six patients received two cycles of the antibody (15 days apart), and nine patients received a four-week cycle treatment.

Comparing the levels of T cells in the blood at the start of treatment (baseline) and six months after, researchers observed differences in T-cell subtypes found in the rituximab-treated group. CD4-positive and interleukin 4 (IL-4)-producing T cells were significantly reduced with rituximab treatment. This decrease was also reflected at the skin level, where the team observed reduced infiltration of this subtype of T cell by looking at skin biopsies.

These findings carry clinical significance, as CD4-positive and IL-4-producing T cells have been involved in fibrotic processes in the heart, liver, kidneys, and brain, researchers noted.

Furthermore, the team saw that CD4-positive and CD40L-positive T cells in the blood were also reduced with rituximab treatment. CD40L is associated with the activation of T-helper cells, which may help shut down an aberrant immune response.

“This study provides experimental evidence that could directly or indirectly indicate that B-cell depletion treatment in patients with SSc may have a further than B-cell depletion role in a target organ such as the skin by altering non-B cell lymphocytic subpopulations,” researchers stated.

The results support that rituximab could be a promising treatment for SSc patients failing to respond to standard-of-care therapies.