High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies

• 成果类型: Article
• 署名作者: Gervais, Adrian; Marchal, Astrid; Maillard, Alexis; Le Voyer, Tom; Rosain, Jeremie; Philippot, Quentin; Bizien, Lucy; Peel, Jessica; Cederholm, Axel; Migaud, Melanie; Pons, Sylvie; Saker, Kahina; Laforet, Pascal; Aubart, Melodie; Gitiaux, Cyril; Biggs, Catherine M.; Lopez, Rafael Leon; Souvannanorath, Sarah; Tard, Celine; Pakleza, Aleksandra Nadaj; Grapperon, Aude-Marie; Heming, Nicholas; Annane, Djillali; Verschueren, Annie; Attarian, Shahram; Bigaut, Kevin; Hankiewicz, Karolina; Kouton, Ludivine; Villar-Quiles, Rocio-Nur; Cauquil, Cecile; Fleury, Marie-Celine; Rocher, Emilie; Nicolas, Guillaume; de Paula Estephan, Eduardo; da Penha Ananias Morita, Maria; Zanoteli, Edmar; Saied, Zakaria; Rachdi, Amine; Rim, Amouri; Belal, Samir; Ben Sassi, Samia; Hubers, Annemarie; Faure, Emmanuel; Desguerre, Isabelle; Basse, Clemence; Girard, Nicolas; Beziat, Vivien; Pan-Hammarstrom, Qiang; Hammarstrom, Lennart; Bodansky, Aaron; Parent, Audrey V.; Anderson, Mark S.; DeRisi, Joseph L.; Demeret, Sophie; Truffault, Frederique; Fort, Romain; Ader, Florence; Wallet, Florent; Trouillet-Assant, Sophie; Abel, Laurent; Molina, Thierry; Alyanakian, Marie-Alexandra; Le Panse, Rozen; Sole, Guilhem; Cobat, Aurelie; Landegren, Nils; Casanova, Jean-Laurent; Puel, Anne; Bastard, Paul; Jouanguy, Emmanuelle
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Necker-Enfants Malades - APHP; Rockefeller University; Uppsala University; CHU Lyon; Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CNRS - National Institute for Biology (INSB); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Raymond-Poincare - APHP; Universite Paris Saclay; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; University of British Columbia; BC Children's Hospital; Hospital Universitario Reina Sofia - Cordoba; Assistance Publique Hopitaux Paris (APHP); Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Hopital Universitaire Henri-Mondor - APHP; Universite de Lille; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Lille; CHU Strasbourg; Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; Hopital Universitaire Pitie-Salpetriere - APHP; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bicetre - APHP; Universidade de Sao Paulo; Universite de Tunis-El-Manar; Institut National de Neurologie; Faculte de Medecine de Tunis (FMT); Universite de Tunis-El-Manar; Institut National de Neurologie; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; Hopital Universitaire Charles-Foix - APHP; Hopital Universitaire Pitie-Salpetriere - APHP; UNICANCER; Universite PSL; Institut Curie; Universite Paris Saclay; Karolinska Institutet; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Chan Zuckerberg Initiative (CZI); Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite; CHU Lyon; CHU Lyon; CHU Lyon; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite de Bordeaux; CHU Bordeaux; Universite de Bordeaux; Howard Hughes Medical Institute; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Necker-Enfants Malades - APHP
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2518581123
• 发表日期: 2026-08-04
• 页码: e2518581123
• 关键词: autoantibodies; interferons; myasthenia gravis; Covid-19; RAG DEFICIENCY; THYMOMA; autoimmunity; antibodies; mutations; alpha

摘要

Patients with myasthenia gravis (MG) may produce autoantibodies neutralizing type I interferons (AAN-I-IFN), which underlie severe viral diseases, including critical COVID-19 pneumonia, in patients without MG. We studied an international cohort of 85 unvaccinated SARS-CoV-2-infected MG patients not given antiviral treatment. Hypoxemic pneumonia occurred in 48 of these patients, including 22 (45.8%) with AAN-I-IFN, which neutralized both IFN-alpha 2 and IFN-omega in 14 (29.2%) patients. Six (16.2%) of the remaining 37 patients had AAN-I-IFN, neutralizing both IFN-alpha 2 and IFN-omega in three patients. The risk of hypoxemic pneumonia was greater in MG patients with AAN-I-IFN neutralizing 10 ng/mL of both IFN-alpha 2 and IFN-omega (odds ratio and 95% confidence interval (OR [95% CI]): 12.7 [2.1 to 78.9], P = 0.0010) or IFN-alpha 2 at any dose (OR [95% CI]: 4.7 [1.5 to 15.0], P = 0.0054) than in those without such autoantibodies. The risk of producing AAN-I-IFN was much higher in MG patients than in the general population (OR [95% CI]: 28.9 [10.8 to 77.7], P = 4.9 & times; 10-27). Thymoma was found in 14 patients and increased the risk of AAN-I-IFN (64% versus 27%, (OR [95% CI]: 5.6 [1.6 to 19.4], P = 0.0050) and hypoxemic pneumonia (9.2 [1.9 to 44.2]; P = 0.0019). Thymoma is, thus, associated with a higher risk of producing AAN-I-IFN, which are, in turn, associated with a higher risk of developing life-threatening COVID-19 pneumonia in patients with MG.