Treatment Monitoring and Outcome Prediction in Invasive Aspergillosis using Immunologic Markers.

BACKGROUND: Invasive aspergillosis (IA) is a leading cause of mortality despite antifungal therapy. Current biomarkers for treatment monitoring and outcome prediction are limited, with host biomarkers showing potential in other fungal diseases but not in IA yet. Here, we aimed to identify circulating immunological biomarkers for treatment monitoring and outcome prediction for IA.

METHODS: In this European Confederation of Medical Mycology (ECMM) multicenter study, we prospectively evaluated a cohort of 51 patients with probable or proven IA with underlying hematological malignancies. Serial serum samples, collected over a three-week period, were analyzed using the Olink Target 96 Inflammation panel. Differential expression analyses were performed to identify potential biomarkers associated treatment responses at days 7 and 30, in addition to survival analysis for outcome prediction.

RESULTS: During the first days of treatment, all significantly differentially expressed proteins were upregulated in patients showing clinical improvement compared to those with worsening disease, with the exception of CCL23. Multiple proteins significantly correlated with the need to switch from primary to salvage antifungal therapy. For late treatment response, MMP-10 emerged as predictor, with consistent lower expression levels in patients demonstrating clinical improvement during weeks 2 and 3. Moreover, low serum concentrations of CXCL6 at week 2 and MMP-10 at week 3 were associated with higher survival probability.

CONCLUSIONS: The dynamic regulation of immune markers in different disease states the use in predicting responses to antifungal treatment, depending on the goal of the assessment. Future studies should validate these biomarkers and establish their usefulness in clinical practice.

© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PMID: 41778487