Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study
BackgroundSARS-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).MethodsWe...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296273/full |
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| author | Hassen Kared Hassen Kared Hassen Kared Ingrid Jyssum Ingrid Jyssum Amin Alirezaylavasani Amin Alirezaylavasani Amin Alirezaylavasani Ingrid M. Egner Ingrid M. Egner Ingrid M. Egner Trung The Tran Trung The Tran Trung The Tran Lisa Tietze Lisa Tietze Lisa Tietze Katrine Persgård Lund Katrine Persgård Lund Katrine Persgård Lund Anne Therese Tveter Sella A. Provan Hilde Ørbo Espen A. Haavardsholm John Torgils Vaage John Torgils Vaage Kristin Jørgensen Silje Watterdal Syversen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Guro Løvik Goll Ludvig A. Munthe Ludvig A. Munthe |
| author_facet | Hassen Kared Hassen Kared Hassen Kared Ingrid Jyssum Ingrid Jyssum Amin Alirezaylavasani Amin Alirezaylavasani Amin Alirezaylavasani Ingrid M. Egner Ingrid M. Egner Ingrid M. Egner Trung The Tran Trung The Tran Trung The Tran Lisa Tietze Lisa Tietze Lisa Tietze Katrine Persgård Lund Katrine Persgård Lund Katrine Persgård Lund Anne Therese Tveter Sella A. Provan Hilde Ørbo Espen A. Haavardsholm John Torgils Vaage John Torgils Vaage Kristin Jørgensen Silje Watterdal Syversen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Guro Løvik Goll Ludvig A. Munthe Ludvig A. Munthe |
| author_sort | Hassen Kared |
| collection | DOAJ |
| description | BackgroundSARS-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).MethodsWe 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.FindingsThe 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.InterpretationSARS-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. |
| first_indexed | 2024-03-07T23:07:33Z |
| format | Article |
| id | doaj.art-e11ef42f2e654fa5a719bde554fca304 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T23:07:33Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e11ef42f2e654fa5a719bde554fca3042024-02-22T04:32:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.12962731296273Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort studyHassen Kared0Hassen Kared1Hassen Kared2Ingrid Jyssum3Ingrid Jyssum4Amin Alirezaylavasani5Amin Alirezaylavasani6Amin Alirezaylavasani7Ingrid M. Egner8Ingrid M. Egner9Ingrid M. Egner10Trung The Tran11Trung The Tran12Trung The Tran13Lisa Tietze14Lisa Tietze15Lisa Tietze16Katrine Persgård Lund17Katrine Persgård Lund18Katrine Persgård Lund19Anne Therese Tveter20Sella A. Provan21Hilde Ørbo22Espen A. Haavardsholm23John Torgils Vaage24John Torgils Vaage25Kristin Jørgensen26Silje Watterdal Syversen27Fridtjof Lund-Johansen28Fridtjof Lund-Johansen29Fridtjof Lund-Johansen30Guro Løvik Goll31Ludvig A. Munthe32Ludvig A. Munthe33Department of Immunology, Oslo University Hospital, Oslo, NorwayKG Jebsen Centre for B cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayKG Jebsen Centre for B cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayKG Jebsen Centre for B cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayImmunoLingo Convergence Center, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayImmunoLingo Convergence Center, University of Oslo, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayKG Jebsen Centre for B cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Gastroenterology, Akershus University Hospital, Lørenskog, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayPrecision Immunotherapy Alliance, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayImmunoLingo Convergence Center, University of Oslo, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Immunology, Oslo University Hospital, Oslo, NorwayKG Jebsen Centre for B cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayBackgroundSARS-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).MethodsWe 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.FindingsThe 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.InterpretationSARS-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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296273/fullT cellB cellCOVID-19mRNA vaccinationrheumatoid arthritisrituximab |
| spellingShingle | Hassen Kared Hassen Kared Hassen Kared Ingrid Jyssum Ingrid Jyssum Amin Alirezaylavasani Amin Alirezaylavasani Amin Alirezaylavasani Ingrid M. Egner Ingrid M. Egner Ingrid M. Egner Trung The Tran Trung The Tran Trung The Tran Lisa Tietze Lisa Tietze Lisa Tietze Katrine Persgård Lund Katrine Persgård Lund Katrine Persgård Lund Anne Therese Tveter Sella A. Provan Hilde Ørbo Espen A. Haavardsholm John Torgils Vaage John Torgils Vaage Kristin Jørgensen Silje Watterdal Syversen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Fridtjof Lund-Johansen Guro Løvik Goll Ludvig A. Munthe Ludvig A. Munthe Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study Frontiers in Immunology T cell B cell COVID-19 mRNA vaccination rheumatoid arthritis rituximab |
| title | Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study |
| title_full | Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study |
| title_fullStr | Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study |
| title_full_unstemmed | Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study |
| title_short | Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study |
| title_sort | dynamics of sars cov 2 immunity after vaccination and breakthrough infection in rituximab treated rheumatoid arthritis patients a prospective cohort study |
| topic | T cell B cell COVID-19 mRNA vaccination rheumatoid arthritis rituximab |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296273/full |
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