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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.
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.
  • Mageau A; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France; Infection, Antimicrobiens, Modé
  • Tchen J; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France.
  • Ferré VM; Infection, Antimicrobiens, Modélisation, évolution (IAME), INSERM UMR 1137, Université Paris Cité, Paris, France; Service de Virologie, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • Nicaise-Roland P; Service d'Immunologie Autoimmunité, hypersensibilités et biothérapies Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Paris, France; Université Paris Cité, Inserm, PHERE, F-75018, Paris, France.
  • Descamps D; Infection, Antimicrobiens, Modélisation, évolution (IAME), INSERM UMR 1137, Université Paris Cité, Paris, France; Service de Virologie, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • Delory N; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • François C; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • Mendes C; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • Papo T; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France.
  • Goulenok T; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
  • Charles N; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France.
  • Sacré K; Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France. Electronic address: karim.sacre
J Autoimmun ; 134: 102987, 2023 01.
Article in English | MEDLINE | ID: covidwho-2159182
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lupus Erythematosus, Systemic Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: J Autoimmun Journal subject: Allergy and Immunology Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lupus Erythematosus, Systemic Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: J Autoimmun Journal subject: Allergy and Immunology Year: 2023 Document Type: Article