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Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune-modifying therapies
Samuel D. Klebanoff, Lauren B. Rodda, Chihiro Morishima, Mark H. Wener, Yevgeniy Yuzefpolskiy, Estelle Bettelli, Jane H. Buckner, Cate Speake, Marion Pepper, Daniel J. Campbell
Samuel D. Klebanoff, Lauren B. Rodda, Chihiro Morishima, Mark H. Wener, Yevgeniy Yuzefpolskiy, Estelle Bettelli, Jane H. Buckner, Cate Speake, Marion Pepper, Daniel J. Campbell
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Research Article Vaccines

Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune-modifying therapies

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter the response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of patients with RA after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the cytotoxic T lymphocyte antigen 4–Ig therapy abatacept had reduced levels of SARS-CoV-2–neutralizing antibodies after vaccination. At the cellular level, these patients showed reduced activation and class switching of SARS-CoV-2–specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2–specific CD4+ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B cell–depleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in patients with RA on different immune-modifying therapies and help inform efforts to improve vaccination strategies in this vulnerable population.

Authors

Samuel D. Klebanoff, Lauren B. Rodda, Chihiro Morishima, Mark H. Wener, Yevgeniy Yuzefpolskiy, Estelle Bettelli, Jane H. Buckner, Cate Speake, Marion Pepper, Daniel J. Campbell

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Figure 3

MTX and abatacept reduce S-specific memory T cell responses after vaccination.

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MTX and abatacept reduce S-specific memory T cell responses after vaccin...
(A) Representative gating of CD3+CD45RA–CD4+ T cells for AIM+ (CD69+CD137+) within indicated stimulation conditions. (B) Quantification of AIM expression by patient groups as percentage of CD3+CD45RA–CD4+ cells. (C) Representative gating of central memory (CD45RA–CD27+), effector memory (CD45RA–CD27–), and Temra (CD45RA+CD27+) within non-naive and AIM+ T cells. (D) Quantification of CD4+ memory subsets within S protein–stimulated AIM+ cells. (E) Representative gating of CXCR5+ (containing the Tfh population), Th1 (CXCR3+CCR6–), Th17 (CXCR3–CCR6+), Th1/17 (CXCR3+CCR6+), and Th2 (CXCR3–CCR6–CCR4+) cells. (F) Pie charts showing percentage of spike-stimulated AIM+CD4+ T cells falling into each Th subset. Error bars represent mean ± SD. Statistics determined by Kruskal-Wallis test with post hoc Dunn’s multiple-comparison test. All statistically significant comparisons (P < 0.05) between treatment groups are shown. **P < 0.01.

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