Circulating microRNA profiles associated with tick bite and debilitating symptom complexes attributed to ticks...

Tick bites in Australia are associated with a poorly understood syndrome known as Debilitating Symptom Complexes Attributed to Ticks (DSCATT), however, the underlying biological mechanisms remain unclear. Here, we investigate host responses to tick bite and DSCATT by profiling circulating host-encoded microRNAs (miRNAs), key regulators of gene expression. Circulating miRNAs were profiled in two cohorts: a longitudinal cohort followed from tick bite for up to 12 months, and a retrospective cohort with DSCATT. Differential expression analysis revealed that tick bite induces widespread changes in circulating miRNAs, with 149 miRNAs showing significant variation over 12 months. Temporal clustering revealed two expression patterns: one oscillating trajectory and a declining then stabilising, with predicted targets enriched for pathways related to immune modulation, tissue remodelling and cellular stress responses. DSCATT patients exhibited 98 differentially expressed miRNAs, including significant overlap with acute tick bite miRNAs, and four miRNAs correlated with symptom severity, including fatigue and dizziness. Machine learning analysis identified a five-miRNA signature that classified acute tick bite with 86% accuracy and receiver operating characteristic area under the curve (ROC AUC) of 0.92. These findings represent, to the best of our knowledge, the first characterisation of host miRNA responses to tick bite and DSCATT, highlighting potential biomarkers and mechanisms underlying chronic symptom development.