Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors

Jakob Hjorth von Stemann; Florian Dubois; Violaine Saint-André; Vincent Bondet; Celine Posseme; Bruno Charbit; Lluis Quintana-Murci; Morten Bagge Hansen; Sisse Rye Ostrowski; Darragh Duffy; Milieu Intérieur Consortium

doi:10.1002/eji.202451211

Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors

Eur J Immunol. 2024 Nov 17:e202451211. doi: 10.1002/eji.202451211. Online ahead of print.

Authors

Jakob Hjorth von Stemann¹, Florian Dubois^{2

3}, Violaine Saint-André^{2

4}, Vincent Bondet², Celine Posseme², Bruno Charbit^{2

3}, Lluis Quintana-Murci^{5

6}, Morten Bagge Hansen^{1

7}, Sisse Rye Ostrowski^{1

7}, Darragh Duffy^{2

3}; Milieu Intérieur Consortium

Affiliations

¹ Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
² Translational Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.
³ Cytometry and Biomarkers UTechS, Institut Pasteur, Université Paris Cité, Paris, France.
⁴ Bioinformatics and Biostatistics HUB, Department of Computational Biology, Institut Pasteur, Université Paris Cité, Paris, France.
⁵ Institut Pasteur, CNRS UMR2000, Human Evolutionary Genetics Unit, Université Paris Cité, Paris, France.
⁶ Chair of Human Genomics and Evolution, Collège de France, Paris, France.
⁷ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 39551979
DOI: 10.1002/eji.202451211

Abstract

Autoantibodies against cytokines (c-aAb) have been implicated in the pathophysiology of autoimmune diseases, and a variety of infections. In addition, several independent studies have detected elevated titers of c-aAb in the circulation of healthy individuals. To further understand their impact on immune responses, we measured c-aAb against IFN-α, IFN-γ, CSF2, IL-1α, IL-6, and IL-10 in the plasma of 1000 healthy individuals of the Milieu Intérieur (MI) cohort. Focusing on donors above a defined positive cut-off we observed significant age effects for c-aAb against IL-1α, but no major environmental or lifestyle associated factors were identified. Using TruCulture stimulation data from the MI cohort, we observed a strong association between induced IL-1α and c-aAb levels after LPS stimulation. For several other stimuli, c-aAb against IL-1α and IL-10 were associated with decreased or increased proinflammatory gene expression, respectively. Finally, TruCulture assays supplemented with plasma containing high-titer c-aAb showed a strong influence of anti-IFN-α and anti-IL-6 c-aAb on both baseline and induced gene expression. In summary, this study shows a widespread prevalence of anti-cytokine autoantibodies in healthy donors with impacts on diverse immune responses, suggesting a significant contribution of c-aAb to interindividual immune heterogeneity.

Keywords: antibodies; autoimmunity; cytokines; epidemiology; immunodeficiencies.

Abstract

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