Rituximab Impairs B Cell Response But Not T Cell Response to COVID-19 Vaccine in Autoimmune Diseases

Arthritis Rheumatol. 2022 Jun;74(6):927-933. doi: 10.1002/art.42058. Epub 2022 Mar 29.


Objective: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine.

Methods: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools.

Results: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response.

Conclusion: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / immunology*
  • Autoimmune Diseases* / drug therapy
  • BNT162 Vaccine / immunology*
  • COVID-19 Vaccines / immunology*
  • COVID-19* / prevention & control
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • RNA, Messenger
  • Rituximab / therapeutic use
  • SARS-CoV-2


  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunosuppressive Agents
  • RNA, Messenger
  • Rituximab
  • BNT162 Vaccine