B-cell threshold for COVID-19 vaccine response defined in rituximab-treated patients
medwireNews: Researchers have identified a minimum level of B cells in the peripheral circulation that may serve as a biomarker for response to COVID-19 vaccines among rituximab-treated patients.
The study included 19 individuals treated with rituximab – 16 with rheumatoid arthritis (RA) and three with antineutrophil cytoplasmic antibody-associated vasculitis – as well as 12 RA patients on other immunomodulatory therapies and 30 healthy controls who received messenger RNA and/or viral vector-based vaccines against SARS-CoV-2. The majority of participants received two doses of the Pfizer–BioNTech (BNT162b2) vaccine.
In accordance with previous studies, the researchers report that the humoral response to two vaccine doses was “significantly lower and delayed” among patients versus controls, and these differences were “even more pronounced” in the rituximab group compared with controls.
In the rituximab cohort, patients who generated immunoglobulin (Ig)G antibodies against the SARS-CoV-2 spike protein following vaccination had a significantly higher absolute number and frequency of peripheral B cells than those who did not. The study authors identified 10 B cells/µL, or a B-cell frequency of 0.4% of lymphocytes, as the minimum threshold for an antibody response.
Moreover, B-cell numbers and frequency were significantly associated with anti-spike IgG titers, with an “even more pronounced” correlation between these variables and neutralizing antibody titers, say Thomas Dörner (Charité Universitätsmedizin Berlin, Germany) et al.
“This clearly suggests that humoral protection elicited by vaccination is dependent on the critical availability of B cells in [rituximab] treated patients,” they write in Arthritis & Rheumatology.
The team notes that there was no significant correlation between B-cell numbers and serologic response in RA patients on other treatments or healthy controls, suggesting that the association “is restricted to patients with B cell counts below the lower limits of normal.”
In addition to their findings on antibody responses, Dörner and colleagues also report associations between peripheral B-cell numbers and the T-cell response to vaccination. Specifically, they say that rituximab-treated patients with B-cell numbers below 10 cells/µL had “substantially diminished” circulating T follicular helper cell-like CD4+ T cells, reduced activated CD4+ CD8+ T cells with co-expression of CD38 and HLA-DR, and impaired interferon-gamma secretion by spike-specific CD4+ T cells.
Taken together, the study results “may support optimization of vaccination protocols” for rituximab-treated patients, conclude the researchers.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group
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