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Longitudinal Follow-up Reveals Peripheral Immunological Changes Upon Tick Bite in a-Gal-Sensitized Individuals

Swiontek K1, Fischer J2, Hedin F3, Revets D3, Riel S2, Chakrapani N1, Mackenstedt U4, Biedermann T5, Kuehn A1, Cosma A3, Ollert M1,6, Hilger C1

1Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
2Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
3National Cytometry Platform, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
4Department of Parasitology, Institute of Biology, University of Hohenheim, Stuttgart, Germany
5Department of Dermatology and Allergy Biederstein, School of Medicine and Health, Technical University of Munich, Munich, Germany
6Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark

J Investig Allergol Clin Immunol 2025; Vol. 35(4)
doi: 10.18176/jiaci.1028

Background: α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated.
Objective: To investigate the peripheral immune response to tick bites in humans over time.
Methods: In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry.
Results: A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19+ B cells and B-cell subpopulations, as well as a decrease in γδ CD56+ T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56+ T cells were lower in patients than in controls.
Conclusion: Our study provides evidence of significant changes in several immune cell populations in α-Gal–sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.

Key words: α-Gal syndrome, Galactose-α-1,3-galactose, IgE, Immune phenotyping, Mass cytometry, B cell, γδ T cell, Tick bite