Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

PLoS One. 2017 Jun 30;12(6):e0179981. doi: 10.1371/journal.pone.0179981. eCollection 2017.


Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c-aAb in question. A negative correlation between high levels of IL-6-specific c-aAb and plasma levels of C-reactive protein was observed, indicating cytokine-neutralizing levels of c-aAb in healthy blood donors. There was no substantial correlation between high levels of the five individual c-aAb investigated in this study. These data suggest that autoimmunity against endogenous cytokines is a relatively common phenomenon in healthy individuals, and that predictive factors for high, potentially neutralizing c-aAb levels vary depending on the cytokine in question, and may differ from predictors of general c-aAb presence.

MeSH terms

  • Adult
  • Age Factors
  • Autoantibodies / blood*
  • Blood Donors
  • C-Reactive Protein / metabolism*
  • Cytokines / immunology*
  • Denmark
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Obesity / immunology
  • Reference Values
  • Seroepidemiologic Studies
  • Smoking / immunology


  • Autoantibodies
  • Cytokines
  • Immunoglobulin G
  • C-Reactive Protein

Grants and funding

The Danish Blood Donor Study was funded by: The Danish Council for Independent Research-medical sciences (, grant number: 09-069412); The Danish Administrative Regions (; Bloddonorernes Forskningsfond (; Fonden til Lægevidenskabens Fremme (; The Danish Bio and Genome Bank ( The first author was funded by Rigshospitalet Research Foundation ( None of the funders had any influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.