细胞因子自身抗体改变了健康捐献者的基因表达谱。

IF 4.5 3区 医学 Q2 IMMUNOLOGY European Journal of Immunology Pub Date : 2024-11-17 DOI:10.1002/eji.202451211
Jakob Hjorth von Stemann, Florian Dubois, Violaine Saint-André, Vincent Bondet, Celine Posseme, Bruno Charbit, Lluis Quintana-Murci, Morten Bagge Hansen, Sisse Rye Ostrowski, Darragh Duffy
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摘要

针对细胞因子的自身抗体(c-aAb)与自身免疫性疾病和各种感染的病理生理学有关。此外,一些独立研究还检测到健康人血液循环中的 c-aAb 滴度升高。为了进一步了解它们对免疫反应的影响,我们测量了内部环境(MI)队列中 1000 名健康人血浆中抗 IFN-α、IFN-γ、CSF2、IL-1α、IL-6 和 IL-10 的 c-aAb。针对超过规定阳性临界值的捐献者,我们观察到针对 IL-1α 的 c-aAb 有明显的年龄效应,但没有发现与环境或生活方式相关的主要因素。利用来自 MI 队列的 TruCulture 刺激数据,我们观察到 LPS 刺激后诱导的 IL-1α 与 c-aAb 水平之间存在密切联系。对于其他几种刺激,针对 IL-1α 和 IL-10 的 c-aAb 分别与促炎基因表达的减少或增加有关。最后,用含有高滴度 c-aAb 的血浆进行的 TruCulture 试验表明,抗 IFN-α 和抗 IL-6 c-aAb 对基线和诱导基因表达都有很大影响。总之,这项研究表明,抗细胞因子自身抗体在健康捐献者中广泛存在,并对不同的免疫反应产生影响,这表明 c-aAb 对个体间免疫异质性有重大贡献。
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Cytokine Autoantibodies Alter Gene Expression Profiles of Healthy Donors.

Autoantibodies against cytokines (c-aAb) have been implicated in the pathophysiology of autoimmune diseases, and a variety of infections. In addition, several independent studies have detected elevated titers of c-aAb in the circulation of healthy individuals. To further understand their impact on immune responses, we measured c-aAb against IFN-α, IFN-γ, CSF2, IL-1α, IL-6, and IL-10 in the plasma of 1000 healthy individuals of the Milieu Intérieur (MI) cohort. Focusing on donors above a defined positive cut-off we observed significant age effects for c-aAb against IL-1α, but no major environmental or lifestyle associated factors were identified. Using TruCulture stimulation data from the MI cohort, we observed a strong association between induced IL-1α and c-aAb levels after LPS stimulation. For several other stimuli, c-aAb against IL-1α and IL-10 were associated with decreased or increased proinflammatory gene expression, respectively. Finally, TruCulture assays supplemented with plasma containing high-titer c-aAb showed a strong influence of anti-IFN-α and anti-IL-6 c-aAb on both baseline and induced gene expression. In summary, this study shows a widespread prevalence of anti-cytokine autoantibodies in healthy donors with impacts on diverse immune responses, suggesting a significant contribution of c-aAb to interindividual immune heterogeneity.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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