Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study

• Published in: Journal of clinical immunology 2020-02, Vol.40 (2), p.367-377
• Main Authors: von Stemann, Jakob H., Pedersen, Ole B., Hjalgrim, Henrik, Erikstrup, Christian, Ullum, Henrik, Thørner, Lise W., Larsen, Margit AH, Burgdorf, Kristoffer S., Sørensen, Erik, Hansen, Morten B., Ostrowski, Sisse R.
• Format: Article
• Language: English
• Subjects: Antimicrobial agents; Autoantibodies; Biomedical and Life Sciences; Biomedicine; Blood donors; Cytokines; Granulocyte-macrophage colony-stimulating factor; Immunocompetence; Immunodeficiency; Immunology; Immunomodulation; Infectious Diseases; Inflammation; Interleukin 10; Interleukin 6; Internal Medicine; Medical Microbiology; Original; Original Article; α-Interferon
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-020-00744-3

The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1α, IL-6, IL-10, IFNα, and GM-CSF using a Luminex-based multiplex assay, and results were linked to data from the Danish National Prescription Registry. The filing of an antimicrobial prescription following c-aAb measurement was used as a proxy for impaired immunocompetence. We found that c-aAb against pro-inflammatory cytokines IFNα and GM-CSF tended to associate with increased risk of prescription filings in women, whereas antibodies against anti-inflammatory IL-10 were associated with a lower predicted risk of antimicrobial prescriptions, as well as higher self-perceived health scores. We also observed an association of cumulative c-aAb presence with prescription risk. Our data show that cytokine autoantibodies in healthy individuals associate with various proxies for immunomodulation, with the exact association dependent on the pattern of pro- or anti-inflammatory cytokines targeted. This suggests that c-aAb may express cytokine-modulatory properties in healthy individuals and may be critical to further investigate as biomarkers of immunodeficiency.