The Effects of Anti-CD20 Therapy on the Immune Response in Patients with Multiple Sclerosis

April 2022

Previous research has shown that strong cellular immune responses of B-cells and T-cells are correlated with better outcomes in patients infected with SARS-CoV-2. The immune responses in patients who have disorders of the immune system or who take immune-suppressing therapies, however, are not well-described. Anti-CD20 therapies to reduce B-cells to treat autoimmune diseases, such as multiple sclerosis (MS), are known to reduce vaccine responses. Furthermore, it is unclear how therapies against B-cells would affect the T-cell response to vaccination for SARS-CoV-2.

To better understand how patients taking anti-CD20 therapies respond to SARS-CoV-2 vaccines, the investigators measured the humoral and cellular responses to mRNA vaccines in 20 patients with MS treated with ocrelizumab or rituximab compared with 10 healthy controls. Twelve patients with MS treated with anti-CD20 therapies and 8 healthy controls received the BNT162b2 vaccine, and 8 patients with MS treated with anti-CD20 therapies and 2 healthy controls received the mRNA-1273 vaccine. Patients with MS had taken their most recent anti-CD20 treatment an average of 20 days before the first vaccine dose.

The investigators found that 25 to 30 days after the second vaccine dose the antibody response to viral antigens was variable in patients with MS treated with anti-CD20 therapies, whereas all healthy controls had strong responses. Most patients with MS treated with anti-CD20 therapies produced antibodies against the spike antigen, but only half produced antibodies against the receptor-binding domain (RBD). Neutralizing antibodies were also lower in patients with MS treated with anti-CD20 therapies compared with healthy controls, particularly in those who did not have detectable anti-RBD responses.

Patients with MS treated with anti-CD20 therapies had reduced memory B-cell responses as well. All healthy controls had detectable memory B-cells against the spike antigen, but only 30% of patients with MS treated with anti-CD20 therapies had detectable anti-spike memory B-cells. Those who did respond had lower concentrations of these memory B-cells. These results were not surprising given that anti-CD20 therapies suppress B-cells.

All patients with MS treated with anti-CD20 therapies and healthy controls developed antigen-specific CD4 and CD8 T-cell responses to vaccination, but there were differences. The circulating levels of follicular helper T-cells were lower in patients with MS treated with anti-CD20 therapies compared with healthy controls. In contrast, the antigen-specific CD8 T-cell response was stronger in patients with MS treated with anti-CD20 therapies.

The investigators noted that the reduction in follicular helper T-cell responses and increase in CD8 T-cell responses were greatest in patients with MS treated with anti-CD20 therapies who did not have detectable anti-RBD antigens. This observation suggests that a poor antibody response and a lack of B-cells promote a stronger CD8 T-cell response.

The investigators concluded that vaccination is likely to benefit patients taking anti-CD20 therapies because of intact T-cell responses. “Although these T cell responses are promising indicators of immunity in patients with MS treated with anti-CD20, future clinical studies examining the rate of SARS-CoV-2 infection, vulnerability to variants of concern and COVID-19 outcomes in patients with primary and secondary B cell immunodeficiencies will be necessary to fully interrogate the degree of clinical protection in these patients after mRNA vaccination,” the investigators stated.

Source

Apostolidis SA, Kakara M, Painter MM, et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat Med. 2021;27:1990-2001.

Related Items

Subscribe to Value-Based Care in Neurology

Stay up to date with the latest news in neurology by subscribing to receive the free VBCN e‑Newsletter.