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Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α.
Mathian, Alexis; Breillat, Paul; Dorgham, Karim; Bastard, Paul; Charre, Caroline; Lhote, Raphael; Quentric, Paul; Moyon, Quentin; Mariaggi, Alice-Andrée; Mouries-Martin, Suzanne; Mellot, Clara; Anna, François; Haroche, Julien; Cohen-Aubart, Fleur; Sterlin, Delphine; Zahr, Noël; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Amiot, Quentin; Pha, Micheline; Hié, Miguel; Chasset, Francois; Yssel, Hans; Miyara, Makoto; Charneau, Pierre; Ghillani-Dalbin, Pascale; Casanova, Jean-Laurent; Rozenberg, Flore; Amoura, Zahir; Gorochov, Guy.
  • Mathian A; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Institut E3M, Paris, France.
  • Breillat P; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Dorgham K; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Bastard P; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Charre C; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, Paris, France.
  • Lhote R; University of Paris Cité, Imagine Institute, Paris, France.
  • Quentric P; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Moyon Q; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France.
  • Mariaggi AA; Université de Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Virologie, Paris, France.
  • Mouries-Martin S; INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France.
  • Mellot C; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Institut E3M, Paris, France.
  • Anna F; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Haroche J; Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Paris, France.
  • Cohen-Aubart F; Université de Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Virologie, Paris, France.
  • Sterlin D; INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France.
  • Zahr N; Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, service de médecine interne et maladies systémiques (médecine interne 2), Dijon, France.
  • Gervais A; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Le Voyer T; Pasteur-TheraVectys Joint Lab, Institut Pasteur, Paris, France.
  • Bizien L; Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Paris, France.
  • Amiot Q; Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Paris, France.
  • Pha M; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
  • Hié M; Département d'Immunologie, AP-HP, Groupement Hospitalier Pitié-Salpêtrière, Paris, France.
  • Chasset F; Service de Pharmacologie, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, Paris, France.
  • Yssel H; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, Paris, France.
  • Miyara M; University of Paris Cité, Imagine Institute, Paris, France.
  • Charneau P; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, Paris, France.
  • Ghillani-Dalbin P; University of Paris Cité, Imagine Institute, Paris, France.
  • Casanova JL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, Paris, France.
  • Rozenberg F; Département d'Immunologie, AP-HP, Groupement Hospitalier Pitié-Salpêtrière, Paris, France.
  • Amoura Z; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Institut E3M, Paris, France.
  • Gorochov G; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des anti-phospholipides et autres maladies auto-immunes rares, Service de Médecine Interne 2, Institut E3M, Paris, France.
Ann Rheum Dis ; 81(12): 1695-1703, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1992983
ABSTRACT

OBJECTIVES:

Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-ß and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown.

METHODS:

We retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-ß and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns.

RESULTS:

Neutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity.

CONCLUSION:

The production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Herpes Zoster / Lupus Erythematosus, Systemic Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Ann Rheum Dis Year: 2022 Document Type: Article Affiliation country: Ard-2022-222549

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Herpes Zoster / Lupus Erythematosus, Systemic Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Ann Rheum Dis Year: 2022 Document Type: Article Affiliation country: Ard-2022-222549