Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients : a prospective cohort study
Copyright © 2024 Kared, Jyssum, Alirezaylavasani, Egner, The Tran, Tietze, Lund, Tveter, Provan, Ørbo, Haavardsholm, Vaage, Jørgensen, Syversen, Lund-Johansen, Goll and Munthe..
Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI).
Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays.
Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells.
Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 08., Seite 1296273 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kared, Hassen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 01.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2024.1296273 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369448014 |
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| 245 | 1 | 0 | |a Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients |b a prospective cohort study |
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| 500 | |a Date Revised 01.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Kared, Jyssum, Alirezaylavasani, Egner, The Tran, Tietze, Lund, Tveter, Provan, Ørbo, Haavardsholm, Vaage, Jørgensen, Syversen, Lund-Johansen, Goll and Munthe. | ||
| 520 | |a Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI) | ||
| 520 | |a Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays | ||
| 520 | |a Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells | ||
| 520 | |a Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a B cell | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a T cell | |
| 650 | 4 | |a breakthrough infection | |
| 650 | 4 | |a mRNA vaccination | |
| 650 | 4 | |a rheumatoid arthritis | |
| 650 | 4 | |a rituximab | |
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| 700 | 1 | |a Alirezaylavasani, Amin |e verfasserin |4 aut | |
| 700 | 1 | |a Egner, Ingrid M |e verfasserin |4 aut | |
| 700 | 1 | |a The Tran, Trung |e verfasserin |4 aut | |
| 700 | 1 | |a Tietze, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Lund, Katrine Persgård |e verfasserin |4 aut | |
| 700 | 1 | |a Tveter, Anne Therese |e verfasserin |4 aut | |
| 700 | 1 | |a Provan, Sella A |e verfasserin |4 aut | |
| 700 | 1 | |a Ørbo, Hilde |e verfasserin |4 aut | |
| 700 | 1 | |a Haavardsholm, Espen A |e verfasserin |4 aut | |
| 700 | 1 | |a Vaage, John Torgils |e verfasserin |4 aut | |
| 700 | 1 | |a Jørgensen, Kristin |e verfasserin |4 aut | |
| 700 | 1 | |a Syversen, Silje Watterdal |e verfasserin |4 aut | |
| 700 | 1 | |a Lund-Johansen, Fridtjof |e verfasserin |4 aut | |
| 700 | 1 | |a Goll, Guro Løvik |e verfasserin |4 aut | |
| 700 | 1 | |a Munthe, Ludvig A |e verfasserin |4 aut | |
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