Tick Saliva Proteins as Potential Inducers of Th2 Responses in Alpha-Gal Syndrome 3434

Abstract Description Alpha-Gal syndrome (AGS) is a delayed form of anaphylaxis triggered by red meat consumption, caused by IgE antibodies against galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal typically occurs after a tick bite, but the mechanisms underlying this sensitization and the tick saliva components involved remain unclear. In this study, we aimed to identify α-Gal-carrying proteins in tick saliva that are recognized by Th2 cells from AGS patients. We hypothesize that these proteins act as hapten-carriers, promoting allergic responses after tick exposure. Proteins were purified from tick salivary glands and saliva, then used to stimulate peripheral blood mononuclear cells (PBMCs) from AGS patients and healthy individuals. Flow cytometry analysis revealed that tick proteins induce proliferation of Th2 cells from AGS patients but not from healthy controls. Proteins that stimulated Th2 responses were identified by peptide mass spectrometry. Based on this finding, the mechanisms of allergic sensitization to tick saliva are also being investigated using human immune organoids. Interim results suggest that α-Gal-containing tick proteins preferentially activate Th2 cells in AGS patients, supporting their role as hapten-carriers driving allergic sensitization. Funding Sources Austrian Science Fund (FWF); Max Kade Foundation Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)