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 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.
Highlights
Materials and MethodsCytokines are pivotal signaling molecules in the immune system balancing pro- and anti-inflammatory immune responses [1]
We have previously reported that detectable levels of cytokine-specific autoantibodies (c-aAb) are common among healthy individuals, with high levels being associated with older age and male sex
Men were significantly older than women and had a significantly higher mental component score (MCS), IL-1α c-aAb, and IL-10 c-aAb, whereas women had higher levels of IL-6 c-aAb (p = 0.0016) and higher body mass index (BMI) and filled more antibacterial prescriptions within 1year follow-up
Summary
Materials and MethodsCytokines are pivotal signaling molecules in the immune system balancing pro- and anti-inflammatory immune responses [1]. The influence of c-aAb on the systemic cytokine networks remains mostly unknown, though multiple studies have linked specific c-aAb to various pathologies and opportunistic infections [6,7,8]. Granulocytemacrophage colony-stimulating factor (GM-CSF) c-aAb have been identified as a causal factor for pulmonary alveolar proteinosis (PAP), a rare and debilitating respiratory disease [9, 10]. C-aAb against pro-inflammatory interleukins (IL) have been associated with improved prognosis or reduced symptoms in some autoimmune diseases, such as rheumatoid arthritis and Sjögrens syndrome indicating that the biologic effect of c-aAb depends on the specific pathological context combined with the c-aAb specificity [12, 13]
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