Department of Hematology, University Hospitals Leuven, Leuven, Belgium.
Department of Microbiology, Immunology and Transplantation, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Mycopathologia. 2024 Feb 26;189(2):24. doi: 10.1007/s11046-024-00831-8.
Invasive aspergillosis (IA) is a major cause of mortality in immunocompromised patients and it is difficult to diagnose because of the lack of reliable highly sensitive diagnostics. We aimed to identify circulating immunological markers that could be useful for an early diagnosis of IA.
We collected longitudinally serum samples from 33 cases with probable/proven IA and two matched control cohorts without IA (one with microbiological and clinical evidence of bacterial or viral non-fungal pneumonia and one without evidence of infection, all matched for neutropenia, primary underlying disease, and receipt of corticosteroids/other immunosuppressants) at a tertiary university hospital. In addition, samples from an independent cohort (n = 20 cases of proven/probable IA and 20 matched controls without infection) were obtained. A panel of 92 circulating proteins involved in inflammation was measured by proximity extension assay. A random forest model was used to predict the development of IA using biomarkers measured before diagnosis.
While no significant differences were observed between IA cases and infected controls, concentrations of 30 inflammatory biomarkers were different between cases and non-infected controls, of which nine were independently replicated: PD-L1, MMP-10, Interleukin(IL)-10, IL-15RA, IL-18, IL-18R1, CDCP1, CCL19 and IL-17C. From the differential abundance analysis of serum samples collected more than 10 days before diagnosis and at diagnosis, increased IL-17C concentrations in IA patients were replicated in the independent cohort.
An increased circulating concentration of IL-17C was detected both in the discovery and independent cohort, both at the time of diagnosis and in samples 10 days before the diagnosis of IA, suggesting it should be evaluated further as potential (early) biomarker of infection.
侵袭性曲霉病（IA）是免疫功能低下患者死亡的主要原因，由于缺乏可靠的高灵敏度诊断方法，因此难以诊断。我们旨在确定可用于 IA 早期诊断的循环免疫标志物。
我们在一家三级大学医院收集了 33 例疑似/确诊 IA 患者的纵向血清样本，以及两个无 IA 的匹配对照组（一组具有细菌或病毒性非真菌性肺炎的微生物学和临床证据，另一组无感染证据，所有对照组均为中性粒细胞减少症、基础疾病和接受皮质类固醇/其他免疫抑制剂）。此外，还从一个独立的队列（n=20 例确诊/疑似 IA 患者和 20 例无感染匹配对照）中获得了样本。通过接近延伸测定法测量了涉及炎症的 92 种循环蛋白的一组标志物。使用基于biomarkers 预测 IA 发展的随机森林模型来测量诊断前的biomarkers。
IA 病例与感染对照组之间未观察到显著差异，但是病例与未感染对照组之间的 30 种炎症生物标志物浓度存在差异，其中 9 种差异具有统计学意义：PD-L1、MMP-10、白细胞介素（IL）-10、IL-15RA、IL-18、IL-18R1、CDCP1、CCL19 和 IL-17C。从在诊断前 10 天以上和诊断时收集的血清样本的差异丰度分析中，在独立队列中复制了 IA 患者的 IL-17C 浓度增加。
在发现和独立队列中，无论是在诊断时还是在 IA 诊断前 10 天的样本中，均检测到循环 IL-17C 浓度增加，表明它应该进一步评估为感染的潜在（早期）生物标志物。
