B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab
Open Access
- 22 July 2021
- preprint content
- research article
- Published by Cold Spring Harbor Laboratory
Abstract
Objectives Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy show substantially impaired anti-SARS-CoV-2 vaccine humoral but partly inducible cellular immune responses. However, the complex relationship between antigen-specific B and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown. Methods Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) patients receiving RTX, 12 RA patients on other therapies and 30 healthy controls after SARS-CoV-2 vaccination with either mRNA or vector based vaccines. Results A minimum of 10 B cells/µL in the peripheral circulation was necessary in RTX patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX patients lacking IgG seroconversion showed reduced antigen-specific B cells, lower frequency of TfH-like cells as well as less activated CD4 and CD8 T cells compared to IgG seroconverted RTX patients. Functionally relevant B cell depletion resulted in impaired IFNγ secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients independently of IgG formation. Conclusions Patients receiving rituximab with B cell numbers above 10 B cells/µl were able to mount humoral and more robust cellular responses after SARS-CoV-2 vaccination that may permit optimization of vaccination in these patients. Mechanistically, the data emphasize the crucial role of co-stimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B and plasma cell differentiation.Keywords
This publication has 34 references indexed in Scilit:
- Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19The New England Journal of Medicine, 2021
- BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination SettingThe New England Journal of Medicine, 2021
- Efficacy and Safety of the mRNA-1273 SARS-CoV-2 VaccineThe New England Journal of Medicine, 2021
- Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registryAnnals Of The Rheumatic Diseases, 2021
- COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping ReviewPathogens & Immunity, 2021
- Safety and Efficacy of the BNT162b2 mRNA Covid-19 VaccineThe New England Journal of Medicine, 2020
- Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UKThe Lancet, 2020
- Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort studyArthritis Research & Therapy, 2019
- 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseasesAnnals Of The Rheumatic Diseases, 2019
- Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRDRMD Open, 2019