Journal Article

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

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

2022

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Abatacept / Aldehydes / Antibodies / Antibodies, Viral / antibody response / Antirheumatic Agents - therapeutic use / Arthritis, Rheumatoid - drug therapy / BNT162 Vaccine / CD19 antigen / CD27 antigen / CD4 antigen / Coronaviruses / Corticosteroids / COVID-19 / COVID-19 - prevention & control / COVID-19 Vaccines / CTLA-4 protein / Cytotoxicity / Disease / Drug dosages / Enrollments / Flow cytometry / Humans / Immune response / Immune response (cell-mediated) / Immunity / Immunoglobulin D / Immunoglobulin G / Immunoglobulin M / Immunological memory / Immunology / Immunosuppressive agents / Infections / Kinases / Kinetics / Lymphocytes B / Lymphocytes T / Medical personnel / Memory cells / mRNA / mRNA vaccine / mRNA vaccines / Pandemics / Peptides / Phenotypes / Proteins / Rheumatoid arthritis / RNA, Messenger / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / T-cell response / T-Lymphocytes / Vaccination / Vaccines / whole blood / γ-Interferon