Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

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. Following vaccine completed schedule, health care workers (HCWs,...

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Vydáno v:Frontiers in immunology Ročník 13; s. 846753
Hlavní autoři: Farroni, Chiara, Picchianti-Diamanti, Andrea, Aiello, Alessandra, Nicastri, Emanuele, Laganà, Bruno, Agrati, Chiara, Castilletti, Concetta, Meschi, Silvia, Colavita, Francesca, Cuzzi, Gilda, Casetti, Rita, Grassi, Germana, Petrone, Linda, Vanini, Valentina, Salmi, Andrea, Repele, Federica, Altera, Anna Maria Gerarda, Maffongelli, Gaetano, Corpolongo, Angela, Salemi, Simonetta, Di Rosa, Roberta, Nalli, Gabriele, Sesti, Giorgio, Vaia, Francesco, Puro, Vincenzo, Goletti, Delia
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 28.02.2022
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ISSN:1664-3224, 1664-3224
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Shrnutí: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. 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. 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 MBCs (CD19 CD27 IgD IgM IgG ), 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 T-cell compartment. 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.
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Edited by: Luca Quartuccio, University of Udine, Italy
Members of INMI COVID-19 Vaccine Study Group are listed in the Acknowledgments section
These authors have contributed equally to this work and share first authorship
This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology
Present address:Concetta Castilletti, Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
Reviewed by: Silvia Piantoni, ASST-Spedali Civili and University of Brescia, Italy; Rossana Domenis, University of Udine, Italy
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.846753