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

ECMM Immunologic Markers for Treatment Monitoring and Diagnosis in Invasive Mold Infection Working Group Contributors, Robina Aerts (Corresponding author), Mihai G. Netea, Martin Hoenigl (Corresponding author)

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Samenvatting

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.

Originele taal-2Engels
Artikelnummer24
Aantal pagina's12
TijdschriftMycopathologia
Volume189
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - apr. 2024

Financiering

Open access funding provided by Medical University of Graz. The study was supported by an Investigator Initiated Research Grant from Gilead Sciences (Project: Immunologic Markers for Treatment Monitoring and Diagnosis in Invasive Mold Infection; IN-EU-131–5720).

FinanciersFinanciernummer
Gilead SciencesIN-EU-131–5720
Medical University of Graz

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