tetano
Editor, Senior Moderator
Front Immunol
. 2022 Feb 28;13:846753.
doi: 10.3389/fimmu.2022.846753. eCollection 2022.
Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis
Chiara Farroni[SUP] 1 [/SUP], Andrea Picchianti-Diamanti[SUP] 2 [/SUP], Alessandra Aiello[SUP] 1 [/SUP], Emanuele Nicastri[SUP] 3 [/SUP], Bruno Laganà[SUP] 2 [/SUP], Chiara Agrati[SUP] 4 [/SUP], Concetta Castilletti[SUP] 5 [/SUP], Silvia Meschi[SUP] 5 [/SUP], Francesca Colavita[SUP] 5 [/SUP], Gilda Cuzzi[SUP] 1 [/SUP], Rita Casetti[SUP] 4 [/SUP], Germana Grassi[SUP] 4 [/SUP], Linda Petrone[SUP] 1 [/SUP], Valentina Vanini[SUP] 1 6 [/SUP], Andrea Salmi[SUP] 1 [/SUP], Federica Repele[SUP] 1 [/SUP], Anna Maria Gerarda Altera[SUP] 1 [/SUP], Gaetano Maffongelli[SUP] 3 [/SUP], Angela Corpolongo[SUP] 3 [/SUP], Simonetta Salemi[SUP] 2 [/SUP], Roberta Di Rosa[SUP] 2 [/SUP], Gabriele Nalli[SUP] 2 [/SUP], Giorgio Sesti[SUP] 2 [/SUP], Francesco Vaia[SUP] 7 [/SUP], Vincenzo Puro[SUP] 8 [/SUP], Delia Goletti[SUP] 1 [/SUP]
Affiliations
Abstract
Objective: To assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies.
Methods: Following vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry.
Results: After 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3-44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9-108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3-260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG[SUP]+[/SUP] MBCs (CD19[SUP]+[/SUP]CD27[SUP]+[/SUP]IgD[SUP]-[/SUP]IgM[SUP]-[/SUP]IgG[SUP]+[/SUP]), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4[SUP]+[/SUP] T-cell compartment.
Conclusions: In this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.
Keywords: COVID-19; DMARD (disease-modifying antirheumatic drug); T-cell response; antibody response; biological therapy; mRNA vaccine; rheumatoid arthritis; whole blood.
. 2022 Feb 28;13:846753.
doi: 10.3389/fimmu.2022.846753. eCollection 2022.
Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis
Chiara Farroni[SUP] 1 [/SUP], Andrea Picchianti-Diamanti[SUP] 2 [/SUP], Alessandra Aiello[SUP] 1 [/SUP], Emanuele Nicastri[SUP] 3 [/SUP], Bruno Laganà[SUP] 2 [/SUP], Chiara Agrati[SUP] 4 [/SUP], Concetta Castilletti[SUP] 5 [/SUP], Silvia Meschi[SUP] 5 [/SUP], Francesca Colavita[SUP] 5 [/SUP], Gilda Cuzzi[SUP] 1 [/SUP], Rita Casetti[SUP] 4 [/SUP], Germana Grassi[SUP] 4 [/SUP], Linda Petrone[SUP] 1 [/SUP], Valentina Vanini[SUP] 1 6 [/SUP], Andrea Salmi[SUP] 1 [/SUP], Federica Repele[SUP] 1 [/SUP], Anna Maria Gerarda Altera[SUP] 1 [/SUP], Gaetano Maffongelli[SUP] 3 [/SUP], Angela Corpolongo[SUP] 3 [/SUP], Simonetta Salemi[SUP] 2 [/SUP], Roberta Di Rosa[SUP] 2 [/SUP], Gabriele Nalli[SUP] 2 [/SUP], Giorgio Sesti[SUP] 2 [/SUP], Francesco Vaia[SUP] 7 [/SUP], Vincenzo Puro[SUP] 8 [/SUP], Delia Goletti[SUP] 1 [/SUP]
Affiliations
- PMID: 35309297
- PMCID: PMC8924958
- DOI: 10.3389/fimmu.2022.846753
Abstract
Objective: To assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies.
Methods: Following vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry.
Results: After 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3-44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9-108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3-260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG[SUP]+[/SUP] MBCs (CD19[SUP]+[/SUP]CD27[SUP]+[/SUP]IgD[SUP]-[/SUP]IgM[SUP]-[/SUP]IgG[SUP]+[/SUP]), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4[SUP]+[/SUP] T-cell compartment.
Conclusions: In this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.
Keywords: COVID-19; DMARD (disease-modifying antirheumatic drug); T-cell response; antibody response; biological therapy; mRNA vaccine; rheumatoid arthritis; whole blood.