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. METHODS: In this 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 3-week period, were analyzed using the Olink Target 96 Inflammation panel. Differential expression analyses and survival analysis for outcome prediction were performed. RESULTS: Early after treatment, all differentially expressed proteins were upregulated in patients showing clinical improvement compared with 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, matrix metalloproteinase-10 (MMP-10) emerged as predictor, with consistently lower expression during 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 dynamics of immune markers across disease states may help predicting responses to antifungal treatment. Future studies should establish their usefulness in clinical practice.