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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1459616
This article is part of the Research Topic Unraveling the Molecular Mechanisms of Cytokine Signaling in Regulating Inflammatory Diseases View all 13 articles

Autoantibodies targeting Interferons and GM-CSF are associated with adverse outcome risk, comorbidities and pathogen in community-acquired pneumonia cohort

Provisionally accepted
Jakob H. Von Stemann Jakob H. Von Stemann 1*Arnold M. Dungu Arnold M. Dungu 2Maria V. Laguarda Maria V. Laguarda 1Camilla Ryrsø Camilla Ryrsø 1,3Maria H. Hegelund Maria H. Hegelund 1Daniel Faurholt-Jepsen Daniel Faurholt-Jepsen 4,5Rikke Krogh-Madsen Rikke Krogh-Madsen 3,6,7Morten B. Hansen Morten B. Hansen 1,7Birgitte Lindegaard Birgitte Lindegaard 2,3,7Sisse R. Ostrowski Sisse R. Ostrowski 1,6
  • 1 Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Capital Region of Denmark, Denmark
  • 2 Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, Hilleroed, Denmark
  • 3 Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark
  • 4 Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Copenhagen, Denmark
  • 5 Department of Clinical medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Copenhagen, Denmark
  • 6 Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
  • 7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark

The final, formatted version of the article will be published soon.

    Abstract Cytokine autoantibodies (c-aAb) have been associated with pulmonary diseases, including severe novel coronavirus (COVID-19) disease and pulmonary alveolar proteinosis. This study aimed to determine c-aAb association with community-acquired pneumonia (CAP) etiology (SARS-CoV-2, influenza, or bacteria), and c-aAb associations to CAP-related clinical outcomes and pulmonary comorbidities. In a cohort of 665 patients hospitalized with CAP, c-aAb targeting IFNα, IFNβ, IFNγ, IL-1α, IL-6, IL-10 and GM-CSF were measured in plasma samples. Associations between c-aAb and baseline characteristics, pulmonary comorbidities, pathogen, intensive care unit (ICU) transferal, time to clinical stability and mortality were estimated, with results stratified by sex. Men infected with SARS-CoV-2 had more high-titer type 1 IFN c-aAb compared to other pathogens. Among patients with CAP, asthma and bronchiectasis comorbidities were associated with high-titer GM-CSF c-aAb in men, and men with high-titer IFNβ c-aAb had increased odds for ICU transferal. High-titer IL-10 c-aAb were associated with faster clinical stability in women. In conclusion, in men with CAP various c-aAb – including type 1 IFN and GM-CSF c-aAb - were associated with adverse clinical events and comorbidities, whereas c-aAb targeting an autoinflammatory cytokine were associated with a positive outcome in women. This suggests that the potentially immunomodulatory effects of c-aAb depend on pathogen, autoantibody-specificity, comorbidity and sex.

    Keywords: Community-acquired pneumonia (CAP), coronavirus disease 2019, Cytokine autoantibody, type 1 interferon, Interleukin-10, granulocyte-macrophage colonystimulating factor

    Received: 04 Jul 2024; Accepted: 04 Oct 2024.

    Copyright: © 2024 Von Stemann, Dungu, Laguarda, Ryrsø, Hegelund, Faurholt-Jepsen, Krogh-Madsen, Hansen, Lindegaard and Ostrowski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jakob H. Von Stemann, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Capital Region of Denmark, Denmark

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.