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.

中文翻译：

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细胞因子自身抗体与感染风险和自我感知健康相关：丹麦献血者研究的结果。

人类中天然存在的细胞因子特异性自身抗体 (c-aAb) 的存在以及与选定病理的关联已得到充分证实。然而，c-aAb 对免疫能力的总体影响在很大程度上仍然未知。在本文中，我们对 c-aAb 与感染风险的关联进行了大规模调查。使用基于 Luminex 的多重检测对一组健康的丹麦献血者进行了 c-aAb 抗 IL-1α、IL-6、IL-10、IFNα 和 GM-CSF 的筛查，结果与丹麦国家实验室的数据相关联处方登记处。在 c-aAb 测量后提交抗菌处方被用作免疫能力受损的代理。我们发现针对促炎细胞因子 IFNα 和 GM-CSF 的 c-aAb 往往与女性处方申请的风险增加有关，而针对抗炎 IL-10 的抗体与较低的抗菌药物处方预测风险以及较高的自我感知健康评分相关。我们还观察到累积 c-aAb 存在与处方风险之间的关联。我们的数据显示，健康个体的细胞因子自身抗体与各种免疫调节代理相关，其确切关联取决于靶向的促炎或抗炎细胞因子的模式。这表明 c-aAb 可能在健康个体中表达细胞因子调节特性，对于进一步研究作为免疫缺陷的生物标志物可能至关重要。我们还观察到累积 c-aAb 存在与处方风险之间的关联。我们的数据显示，健康个体的细胞因子自身抗体与各种免疫调节代理相关，其确切关联取决于靶向的促炎或抗炎细胞因子的模式。这表明 c-aAb 可能在健康个体中表达细胞因子调节特性，对于进一步研究作为免疫缺陷的生物标志物可能至关重要。我们还观察到累积 c-aAb 存在与处方风险之间的关联。我们的数据显示，健康个体的细胞因子自身抗体与各种免疫调节代理相关，其确切关联取决于靶向的促炎或抗炎细胞因子的模式。这表明 c-aAb 可能在健康个体中表达细胞因子调节特性，对于进一步研究作为免疫缺陷的生物标志物可能至关重要。