tetano
Editor, Senior Moderator
Front Immunol
. 2024 Feb 22:15:1296273.
doi: 10.3389/fimmu.2024.1296273. eCollection 2024. Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study
Hassen Kared[SUP] 1 2 3 [/SUP], Ingrid Jyssum[SUP] 4 5 [/SUP], Amin Alirezaylavasani[SUP] 1 2 3 [/SUP], Ingrid M Egner[SUP] 1 2 3 [/SUP], Trung The Tran[SUP] 1 3 6 [/SUP], Lisa Tietze[SUP] 1 3 6 [/SUP], Katrine Persgård Lund[SUP] 1 2 3 [/SUP], Anne Therese Tveter[SUP] 4 [/SUP], Sella A Provan[SUP] 4 [/SUP], Hilde Ørbo[SUP] 4 [/SUP], Espen A Haavardsholm[SUP] 4 [/SUP], John Torgils Vaage[SUP] 1 4 [/SUP], Kristin Jørgensen[SUP] 7 [/SUP], Silje Watterdal Syversen[SUP] 4 [/SUP], Fridtjof Lund-Johansen[SUP] 1 3 6 [/SUP], Guro Løvik Goll[SUP] #[/SUP][SUP] 4 [/SUP], Ludvig A Munthe[SUP] #[/SUP][SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: ACPA; B cell; COVID-19; T cell; breakthrough infection; mRNA vaccination; rheumatoid arthritis; rituximab.
. 2024 Feb 22:15:1296273.
doi: 10.3389/fimmu.2024.1296273. eCollection 2024. Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study
Hassen Kared[SUP] 1 2 3 [/SUP], Ingrid Jyssum[SUP] 4 5 [/SUP], Amin Alirezaylavasani[SUP] 1 2 3 [/SUP], Ingrid M Egner[SUP] 1 2 3 [/SUP], Trung The Tran[SUP] 1 3 6 [/SUP], Lisa Tietze[SUP] 1 3 6 [/SUP], Katrine Persgård Lund[SUP] 1 2 3 [/SUP], Anne Therese Tveter[SUP] 4 [/SUP], Sella A Provan[SUP] 4 [/SUP], Hilde Ørbo[SUP] 4 [/SUP], Espen A Haavardsholm[SUP] 4 [/SUP], John Torgils Vaage[SUP] 1 4 [/SUP], Kristin Jørgensen[SUP] 7 [/SUP], Silje Watterdal Syversen[SUP] 4 [/SUP], Fridtjof Lund-Johansen[SUP] 1 3 6 [/SUP], Guro Løvik Goll[SUP] #[/SUP][SUP] 4 [/SUP], Ludvig A Munthe[SUP] #[/SUP][SUP] 1 2 [/SUP]
Affiliations
- PMID: 38455062
- PMCID: PMC10917913
- DOI: 10.3389/fimmu.2024.1296273
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.
Keywords: ACPA; B cell; COVID-19; T cell; breakthrough infection; mRNA vaccination; rheumatoid arthritis; rituximab.