B-cell Levels May Predict COVID Vaccine Response in Patients on Rituximab
An appropriate immune response to COVID-19 vaccines among people with ANCA-associated vasculitis (AAV) and rheumatoid arthritis (RA) treated with rituximab seems to be dependent on the number of B-cells, a study found.
Rituximab, sold as Rituxan among others, is an antibody treatment that targets the CD20 protein at the surface of immune B-cells, thereby reducing their numbers. B-cells are specific immune cells involved in antibody production, being also responsible for the self-reacting antibodies that cause autoimmune diseases such as AAV and RA.
However, B-cells are needed for mounting long-lasting immune responses after a vaccine, such as the COVID-19 vaccines. Thus, rituximab and other therapies that lower the numbers of these immune cells have been extensively associated with poor COVID-19 outcomes and worse responses to vaccines.
While this association is well established, some patients receiving rituximab are able to mount an effective response to COVID-19 vaccines. This is often dependent on the time that has passed since a patient received their last rituximab dose at the time of vaccination.
In other words, if a patient received treatment shortly before getting the shot, their immune B-cells haven’t had the time to recover and mount an effective response.
A team of researchers in Germany now set out to determine if there is a specific B-cell threshold that predicts responses to vaccines in people who received rituximab.
Their study included 61 individuals who had received their COVID-19 vaccine between February and May 2021 in Berlin. Among them, 19 patients — 16 with RA and 3 with AAV — had received rituximab. The remaining included 12 RA patients on other therapies (RA group) and 30 healthy people that served as controls.
At the time of vaccination, the median time since last rituximab dose was nine months, and the rituximab group had been receiving B-cell depleting therapy for an average of three years. Their circulating B-cells were between 0 and 484 cells per microliter.
Vaccine responses were assessed six days after the second dose. While all patients in the control group developed antibodies against the virus’ S1 protein, the antibody response was significantly reduced in the RA group and in rituximab-treated patients.
Since research has shown that there may be a delayed immune response to vaccination in people with rheumatic diseases, the researchers examined these immune responses in the two patient groups three to four weeks after full vaccination.
At this point, 83.3% of the RA patients and 68.4% of the patients on rituximab had developed antibodies against SARS-CoV-2, the virus that causes COVID-19.
Additional analyses found that the number of B-cells in circulation predicted vaccine responses in the rituximab group, but not in the other groups, “suggesting that the correlation between B cell numbers and [antibody] response is restricted to patients with B cell counts below the lower limits of normal,” the researchers noted.
In particular, rituximab-treated patients had to have at least 10 B-cells per microliter of blood for a positive immune response to the vaccines. Patients with B-cell numbers below that threshold were found to lack a response to COVID-19 vaccination.
“This clearly suggests that [antibody] protection elicited by vaccination is dependent on the critical availability of B cells in RTX [rituximab] treated patients,” the researchers wrote.
Consistent with the lack of antibody response, people on rituximab who failed to develop antibodies against the vaccine also had lower numbers of B-cells and T-cells that were specifically equipped to fight the virus, the researchers found.
The cytokine response — the secretion of specific molecules by immune cells that help combat the virus — was also diminished in rituximab-treated patients who did not have an antibody response to the virus, showing that a certain number of B-cells is essential for mounting an adequate immune response after COVID-19 vaccines.
“As a clinical consequence, we propose a range of absolute B cells signifying expansion of vaccine responses after RTX treatment, which may support optimization of vaccination protocols among this vulnerable patient group,” the researchers concluded.