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J Med Virol . Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-

tetano

Editor, Senior Moderator
J Med Virol


. 2024 Apr;96(4):e29573.
doi: 10.1002/jmv.29573. Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination

Yong Fan[SUP] 1 [/SUP], Siyuan Huang[SUP] 2 [/SUP], Duo Wu[SUP] 3 [/SUP], Ming Chu[SUP] 4 [/SUP], Juan Zhao[SUP] 1 [/SUP], Jiaying Zhang[SUP] 1 [/SUP], Yu Wang[SUP] 1 [/SUP], Yanni Gui[SUP] 1 [/SUP], Xiaofei Ye[SUP] 3 [/SUP], Guiqiang Wang[SUP] 5 [/SUP], Yan Geng[SUP] 1 [/SUP], Yuedan Wang[SUP] 4 [/SUP], Zhuoli Zhang[SUP] 1 [/SUP]



Affiliations
Abstract

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

Keywords: COVID‐19; booster vaccines; rheumatoid arthritis; single‐cell RNA sequencing.

 
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