Background/Purpose: DMARDs that treat RA may reduce immune responses to COVID-19 vaccination. We compared measures of humoral and cell-mediated immunity in RA patients before and after a 3rd dose of COVID-19 vaccine.

Methods: RA patients that had previously received 2 doses of mRNA vaccine enrolled in a single-center prospective observational study, July-Dec 2021, before receiving a 3rd dose of mRNA vaccine. Subjects self-reported holding or continuing DMARDs; rituximab users were excluded from analysis. RA disease activity (RADAI-5) was self-reported weekly pre- and post-3rd dose. Blood samples were collected pre- and week 4 post-3rd dose. Humoral response was measured with in-house ELISA assays for anti-Spike (anti-S) and anti-receptor binding domain (anti-RBD) IgG in equivalent units to monoclonal antibody positive control; results were log-transformed prior to statistical analyses. We calculated delta and fold-change of anti-S and anti-RBD post- vs. pre-3rd dose. “Healthy response” to the 3rd dose was defined as ELISA within 1 standard deviation of the mean among 6 healthy controls 4-8 weeks after a 2nd dose of mRNA vaccine. Cell-mediated response was assessed in a subset of seropositive RA subjects by incubating PBMCs with SARS-CoV-2 peptide pool (Miltenyi Biotec). Adjusted frequencies of stimulated CD4 T cells expressing < ![if !msEquation] >< ![if !vml] >< ![endif] >< ![endif] >2 activation markers (IFNg, TNF, IL-2, 4-1BB, CD40L, CD69) were compared pre- vs. post-3rd dose. Spearman’s correlations assessed the relationship between ELISA levels and frequencies of activated CD4 T cells. Subgroup analyses compared subjects (a) holding vs. continuing DMARDs and (b) by DMARD group.

Results: Among 60 subjects, mean age was 63 and 88% were female. TNFi (43%) and methotrexate (23%) were the most common DMARDs (Table 1). 57% held at least 1 DMARD around the 3rd dose; baseline RA disease activity did not significantly differ between those holding vs. continuing DMARDs (p=0.58). At week 4 post-3rd dose, a “healthy response” was observed in 38% for anti-S and 45% for anti-RBD. Anti-S ELISA levels increased 1.4-fold among those holding DMARDs and 1.5-fold among those continuing DMARDs (p=0.56); anti-RBD increased 1.6-fold in those holding DMARDs and 1.7-fold in those continuing DMARDs (p=0.76) (Figure 1). Fold-change in anti-S and anti-RBD ELISA were similar when comparing methotrexate to other DMARD groups (p >0.05 for each comparison). Among 26 subjects that provided PBMCs, frequencies of activated CD4 T cells were significantly greater post- vs. pre-3rd dose in both those that held DMARDs (p< 0.01) and those that continued DMARDs (p=0.02) (Table 2). Neither fold-change nor delta ELISA level was significantly correlated with the change in frequency of activated CD4 T cells (rho -0.26 to -0.06, p >0.05).

Conclusion: After a 3rd dose of mRNA COVID vaccine, ELISA levels significantly increased in RA subjects using DMARDs though fewer than half achieved a humoral response on par with healthy controls after a 2nd dose. Change in ELISA levels did not correlate with CD4 T cell responses. Additional studies are needed to determine clinical relevance of quantitative differences in humoral and cell-mediated responses in immunosuppressed patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-humoral-and-cellular-immune-responses-in-persons-with-rheumatoid-arthritis-following-a-third-dose-of-covid-19-vaccine/