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

ObjectiveTo 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.MethodsFollowing 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.ResultsAfter 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.ConclusionsIn 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..

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Frontiers in Immunology - 13(2022)

Sprache:

Englisch

Beteiligte Personen:

Chiara Farroni [VerfasserIn]
Andrea Picchianti-Diamanti [VerfasserIn]
Alessandra Aiello [VerfasserIn]
Emanuele Nicastri [VerfasserIn]
Bruno Laganà [VerfasserIn]
Chiara Agrati [VerfasserIn]
Concetta Castilletti [VerfasserIn]
Silvia Meschi [VerfasserIn]
Francesca Colavita [VerfasserIn]
Gilda Cuzzi [VerfasserIn]
Rita Casetti [VerfasserIn]
Germana Grassi [VerfasserIn]
Linda Petrone [VerfasserIn]
Valentina Vanini [VerfasserIn]
Valentina Vanini [VerfasserIn]
Andrea Salmi [VerfasserIn]
Federica Repele [VerfasserIn]
Anna Maria Gerarda Altera [VerfasserIn]
Gaetano Maffongelli [VerfasserIn]
Angela Corpolongo [VerfasserIn]
Simonetta Salemi [VerfasserIn]
Roberta Di Rosa [VerfasserIn]
Gabriele Nalli [VerfasserIn]
Giorgio Sesti [VerfasserIn]
Francesco Vaia [VerfasserIn]
Vincenzo Puro [VerfasserIn]
Delia Goletti [VerfasserIn]

Links:

doi.org [kostenfrei]
doaj.org [kostenfrei]
www.frontiersin.org [kostenfrei]
Journal toc [kostenfrei]

Themen:

Antibody response
COVID-19
Immunologic diseases. Allergy
MRNA vaccine
Rheumatoid arthritis
T-cell response
Whole blood

doi:

10.3389/fimmu.2022.846753

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

DOAJ035387106