AUTHOR=Von Stemann Jakob Hjorth , Dungu Arnold Matovu , Laguarda Maria Vispe , Ryrsø Camilla Koch , Hegelund Maria Hein , Faurholt-Jepsen Daniel , Krogh-Madsen Rikke , Hansen Morten Bagge , Lindegaard Birgitte , Ostrowski Sisse Rye 

TITLE=Autoantibodies targeting interferons and GM-CSF are associated with adverse outcome risk, comorbidities, and pathogen in community-acquired pneumonia

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1459616

DOI=10.3389/fimmu.2024.1459616

ISSN=1664-3224

ABSTRACT=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.