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B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab
Preprint
in English
| medRxiv
| ID: ppmedrxiv-21260803
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A scientific journal published article is available and is probably based on this preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
ObjectivesPatients 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. MethodsAntibody 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. ResultsA minimum of 10 B cells/{micro}L 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 IFN{gamma} secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients independently of IgG formation. ConclusionsPatients receiving rituximab with B cell numbers above 10 B cells/{micro}l 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.
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Full text:
Available
Collection:
Preprints
Database:
medRxiv
Type of study:
Prognostic study
Language:
English
Year:
2021
Document type:
Preprint