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

Abstract

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 antiinflammatory 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.

Cytokine autoantibodies are stable throughout the haematopoietic stem cell transplantation course and are associated with distinct biomarker and blood cell profiles

“…High-titre c-aAbs are associated with increased age and biological sex, but their exact aetiology is unknown. The cytokine-inhibitory effects of high-titre c-aAbs have been verified in vitro 3 , and recently, we found associations between c-aAbs against pro- and anti-inflammatory cytokines and an altered infection risk in otherwise healthy blood donors 4 . High-titre c-aAbs against interleukin (IL)-6 have also been linked to low levels of IL-6 and CRP, even in healthy blood donors and have been associated with several staphylococcus infection cases 2 , 5 – 7 .…”

Anticytokine Autoantibodies in Infectious Diseases: A Practical Overview

“…However, in a follow-up study on Danish blood donors, it was shown that even in this healthy population the cumulative presence of ACAAs correlated with several proxies for immune function, such as a self-reported health score and antibiotic prescriptions [7]. correlated with several proxies for immune function, such as a self-reported health score and antibiotic prescriptions [7].…”

“…For anti-GM-CSF autoantibodies, it has been shown for example that only high titers correlate with the development of pulmonary alveolar proteinosis and susceptibility to opportunistic infections [ 5 , 6 ]. However, in a follow-up study on Danish blood donors, it was shown that even in this healthy population the cumulative presence of ACAAs correlated with several proxies for immune function, such as a self-reported health score and antibiotic prescriptions [ 7 ].…”