Abstract
Objective: Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy are at higher risk of poor COVID-19 outcomes and show substantially impaired humoral immune response to anti-SARS-CoV-2 vaccine. However, the complex relationship between antigen-specific B cells 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 patients with rheumatoid arthritis (RA) or antineutrophil cytoplasmic antibody-associated vasculitis receiving RTX, 12 patients with RA receiving other therapies, and 30 healthy controls after SARS-CoV-2 vaccination with either messenger RNA or vector-based vaccines.
Results: A minimum of 10 B cells per microliter (0.4% of lymphocytes) in the peripheral circulation appeared to be required for RTX-treated patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX-treated patients who lacked IgG seroconversion showed reduced receptor-binding domain-positive B cells (P = 0.0005), a lower frequency of Tfh-like cells (P = 0.0481), as well as fewer activated CD4 (P = 0.0036) and CD8 T cells (P = 0.0308) compared to RTX-treated patients who achieved IgG seroconversion. Functionally relevant B cell depletion resulted in impaired interferon-γ secretion by spike-specific CD4 T cells (P = 0.0112, r = 0.5342). In contrast, antigen-specific CD8 T cells were reduced in both RA patients and RTX-treated patients, independently of IgG formation.
Conclusion: In RTX-treated patients, a minimum of 10 B cells per microliter in the peripheral circulation is a candidate biomarker for a high likelihood of an appropriate cellular and humoral response after SARS-CoV-2 vaccination. Mechanistically, the data emphasize the crucial role of costimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B cell and plasma cell differentiation.
【초록키워드】 COVID-19, IgG, Vaccine, therapy, Biomarker, Lymphocytes, Vaccines, Antibody Response, outcome, CD4, anti-SARS-CoV-2, rheumatoid arthritis, SARS-CoV-2 vaccine, B cell, T cell, Seroconversion, response, Patient, plasma, Vasculitis, Autoimmune, humoral immune response, patients, function, Therapies, SARS-CoV-2 vaccination, cellular, Frequency, Inflammatory, CD8 T cell, humoral, rheumatic disease, CD4 T cell, peripheral circulation, Messenger RNA, interferon-γ, higher risk, healthy control, complex, secretion, CD4/CD8, cell differentiation, Cell, likelihood, required, receiving, reduced, activated, cytoplasmic, T cell subset, antigen-specific B cell, RTX, 【제목키워드】 SARS-CoV-2, rituximab, response, number,