Impact of BNT162b2 mRNA anti-SARS-CoV-2 vaccine on interferon-alpha production by plasmacytoid dendritic cells and autoreactive T cells in patients with systemic lupus erythematosus: The COVALUS project. Issue 134 (January 2023)

• Record Type: Journal Article
• Authors: Mageau, Arthur; Tchen, John; Ferré, Valentine Marie; Nicaise-Roland, Pascale; Descamps, Diane; Delory, Nicole; François, Chrystelle; Mendes, Celine; Papo, Thomas; Goulenok, Tiphaine; Charles, Nicolas; Sacré, Karim
• Is Part Of: Journal of autoimmunity. Issue 134(2023)
• Publication Date: 2023-01
• Subjects: Systemic lupus erythematosus -- SARS-CoV-2 -- mRNA vaccine -- Plasmacytoid dendritic cells -- Type-1 interferon; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2022.102987
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Objective: To evaluate the specific response of SLE patients to BNT162b2 vaccination and its impact on autoimmunity defined as in vivo production of interferon-alpha (IFNα) by plasmacytoid dendritic cells (pDCs) and autoreactive immune responses. Methods: Our prospective study included SLE patients and healthy volunteers (HV) who received 2 doses of BNT162b2 vaccine 4 weeks apart. Subjects under immunosuppressive drugs or with evidence of prior COVID-19 were excluded. IgG anti-Spike SARS-CoV-2 (anti-S) antibodies, anti-S specific-B cells, anti-S specific T cells, in vivo INF-α production by pDCs, activation marker expression by pDCs and autoreactive anti-nuclear T cells were quantified before first injection, before second injection, and 3 and 6 months after first injection. Results: Vaccinated SLE patients produced significantly lower IgG antibodies and specific B cells against SARS–CoV-2 as compared to HV. In contrast, anti-S T cell response did not significantly differ between SLE patients and HV. Following vaccination, the surface expression of HLA-DR and CD86 and the in vivo production of IFNα by pDCs significantly increased in SLE patients. The boosted expression of HLA-DR on pDCs induced by BNT162b2 vaccine correlated with the overall immune responses against SARS-CoV-2 (anti-S antibodies: r = 0.27 [0.05–0.46], p = 0.02; anti-S B cells: r = 0.19 [-0.03-0.39], p = 0.09); anti-S T cells: r = 0.28 [0.05–0.47], p = 0.016). Eventually, anti-SARS-CoV-2 vaccination was associated with an overall decrease of autoreactive T cells (slope = - 0.00067, p = 0.015). Conclusion: BNT162b2 vaccine induces a transient in vivo activation of pDCs in SLE that contributes to the immune responses against SARS-CoV-2. Unexpectedly BNT162b2 vaccine also dampens the pool of circulating autoreactive T cells, suggesting that vaccination may have a beneficial impact on SLE disease. Highlights: a B cell defect impairs immune protection following anti-SARS-Cov-2 vaccine in SLE. BNT162b2 mRNA induces an in vivo activation of pDCs that contributes to the immune response against SARS-Cov-2 vaccine. BNT162b2 dampens the pool of circulating autoreactive T cells in SLE suggesting that it may have a beneficial impact on SLE.