Alpha-Gal Sensitization Dynamics in Individuals After Tick Bites With or Without Erythema Migrans

α-Gal syndrome (AGS) is an emerging tick-borne disease characterised by the development of specific immunoglobulin E (sIgE) antibodies against galactose-α-1,3-galactose (α-gal), a carbohydrate found in most mammalian species, but not in humans. AGS occurs in individuals with a history of tick bites. Currently, no data exist on α-gal sIgE seroprevalence in the Dutch population, including those with tick bites or erythema migrans (EM). Therefore, this study aimed to determine the rate of α-gal sIgE seroprevalence in the Dutch population, to assess α-gal sIgE seroconversion after tick bites, and to determine the relationship between EM and α-gal sIgE in serum. α-Gal sensitisation rates were assessed in individuals with tick bites (TB), EM, and the general population. Blood samples were collected from TB- and EM-cases at baseline and again after 3 months. Single blood samples from controls were selected from a Dutch population survey. In total, 156 TB-cases, 160 EM-cases, and 316 population controls were included. α-Gal sensitisation rates were 1.9% for population controls and 10.3% and 19.1% for TB- and EM-cases at baseline, respectively (cut-off α-gal sIgE:  ≥ 0.10 kU_A/L). Rates increased to 17.9% for TB-cases, comparable to the 16.9% for EM-cases 3 months after EM-development. Distinct α-gal sensitisation rates were observed between TB- and EM-cases over a 3-month period. TB-cases showed a rising rate, while EM-cases had elevated rates at both time points. This difference is likely due to timing of the tick bite, with TB-cases having a recent bite and EM-cases developing EM days to weeks post-bite. Both groups had higher sensitisation rates than population controls, corroborating the link between tick bites and α-gal sensitisation.