Circulatory Inflammatory Proteins as Early Diagnostic Biomarkers for Invasive Aspergillosis in Patients with Hematologic Malignancies-an Exploratory Study.

IF 3.6 3区 生物学 Q2 MYCOLOGY
Robina Aerts, Isis Ricaño-Ponce, Mariolina Bruno, Toine Mercier, Diletta Rosati, Johan Maertens, Vinod Kumar, Agostinho Carvalho, Mihai G Netea, Martin Hoenigl
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Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Abstract Image

血液系统炎症蛋白作为血液恶性肿瘤患者侵袭性曲霉菌病的早期诊断生物标志物--一项探索性研究。
目的:侵袭性曲霉菌病(IA)是导致免疫力低下患者死亡的一个主要原因,由于缺乏可靠的高灵敏度诊断方法,该病很难诊断。我们的目的是找出有助于早期诊断侵袭性曲霉病的循环免疫标记物:我们在一家三级大学医院纵向采集了 33 例疑似/确诊 IA 病例的血清样本,以及两组未患 IA 的匹配对照组样本(其中一例有微生物学和临床证据证明患有细菌性或病毒性非真菌肺炎,另一例无感染证据,所有样本均与中性粒细胞减少症、原发性基础疾病、皮质类固醇/其他免疫抑制剂的接受情况相匹配)。此外,还从一个独立队列(n = 20 例已证实/可能感染的肺结核病例和 20 例未感染的匹配对照组)中获得了样本。通过近距离延伸测定法测量了92种参与炎症的循环蛋白。采用随机森林模型,利用诊断前测定的生物标志物预测IA的发展:结果:虽然在IA病例和感染对照组之间没有观察到明显差异,但在病例和非感染对照组之间有30种炎症生物标志物的浓度不同,其中9种是独立重复的:PD-L1、MMP-10、白细胞介素(IL)-10、IL-15RA、IL-18、IL-18R1、CDCP1、CCL19和IL-17C。通过对诊断前10多天和诊断时采集的血清样本进行差异丰度分析,IA患者体内IL-17C浓度的增加在独立队列中得到了复制:结论:在IA诊断时和诊断前10天采集的样本中,IL-17C在发现队列和独立队列中的循环浓度都有所增加,这表明IL-17C作为潜在的(早期)感染生物标记物应得到进一步评估。
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来源期刊
Mycopathologia
Mycopathologia 生物-真菌学
CiteScore
6.80
自引率
3.60%
发文量
76
审稿时长
3 months
期刊介绍: Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.
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