ImmunoCAP-Based Detection of Alpha-Gal Syndrome: A Reproducible Diagnostic Protocol for Human Patients

Alpha-GAL syndrome (AGS) is a type of allergy to mammalian meat and other foods or pharmaceuticals made from mammalian substrates. It is an IgE-mediated reaction caused by sensitization to the polysaccharide galactose-α-1,3-galactose (alpha-GAL) found in tick saliva after a previous tick bite. Alpha-GAL is present on proteins of mammals except primates. Sensitization to alpha-GAL in tick saliva predisposes to cross-reactivity following exposure (oral or non-oral) to glycated galactose-α-1,3-galactose proteins, regardless of their origin. Symptoms of varying severity (from dyspepsia to anaphylaxis) appear 3-6 h after exposure (delayed hypersensitivity) and are usually in the presence of a cofactor. Due to the unusual mechanism and source of allergy, the diagnosis of AGHS is difficult and long-lasting. It is estimated that it takes an average of 7 years from the appearance of the first symptoms to the diagnosis of AGS. Diagnostic procedures include a review of the patient's clinical history, a physical examination, and additional tests, such as alpha-GAL-specific immunoglobulin E (sIgE) or, optionally, a basophil activation test (BAT) with alpha-GAL. Alpha-GAL sIgE levels can be measured using screening methods (ImmunoCAP ISAC_E112i or ALEX3) and the quantitative ImmunoCAP method (ThermoFisher Scientific), which is the reference method. Adherence to appropriate diagnostic procedures and careful analysis of clinical data and additional test results is an effective tool for diagnosing AGS and implementing appropriate therapeutic strategies.