Circulating microRNA profiles associated with tick bite-related illness
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. In this study, 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 the time of tick bite for up to 12 months, and a retrospective cohort of patients with DSCATT. Differential expression analysis revealed that tick bite induces widespread changes in circulating miRNAs, with 149 miRNAs showing significant variation over 12 months. Grouping of miRNAs based on their expression changes identified two distinct trends: one oscillating over time and another declining then stabilising, with predicted targets enriched for pathways related to immune modulation, tissue remodelling and cellular responses to stressors. The DSCATT patients exhibited 98 differentially expressed miRNAs, including significant overlap with miRNAs from the acute tick bite cohort and four miRNAs correlated with symptom severity, including fatigue and dizziness. To assess miRNAs as potential biomarkers for tick bite, machine learning identified a five-miRNA signature that classified acute tick bite cases with 83% accuracy (ROC AUC = 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 for early tick bite detection and providing insight into host processes that may underpin chronic symptom development.