Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

Abstract

The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.

Diagnostic Validity of Specific Immunoglobulin E Levels to alpha-gal in Alpha-gal Syndrome: A Cross-Sectional Analysis.

“…Other researchers have proposed an integrative diagnostic methodology that combines medical history with anti-alpha-gal IgE titers in a machine learning algorithm because it is possible that the cutoff value of sIgE that reveals clinical reactivity might not be well determined since AGS can be highly in uenced by the presence of cofactors and the delayed nature of the reaction [13]. Current strategies for diagnosing AGS explained that the relevance of positive testing to alpha-gal sIgE levels with a cut-off value ≥ 0.35 kU/L remains unclear because it is not able to predict the severity of the reactions [14]. Other authors have shown that the cut-off for sIgE to alpha-gal associated with a positive predictive value of > 95% probability of presenting meat allergy was 2.00 kU/L [15].…”

Alpha-gal syndrome and delayed anaphylaxis after ingestion of red meat: A case report

“…In AGS, the onset of symptoms generally occurs from 3 to 6 hours [ 6 , 7 , 10 ] after the ingestion of the meal. Cofactors can determine an interindividual variability and different reactions even in the same individual and are thus confounding factors.…”

“…Our patient tolerates milk, eggs, and other derivatives, so we did not suggest avoiding them, just like Platts-Mills et al [ 6 ] have suggested. If patients are in areas where ticks may be present, we recommend to prevent tick bites that can trigger another allergic reaction (for example by wearing light-colored clothes or applying specific tick repellents, such as permethrin) [ 7 , 11 ].…”

Evolution of Tick Vaccinology Highlights Changes in Paradigms in This Research Area

“…Ticks are blood-feeding arthropod ectoparasites affecting human and animal health worldwide [ 1 , 2 , 3 ]. Ticks are vectors of pathogens and are associated with allergic pathologies, such as the alpha-gal syndrome [ 2 , 4 ]. Vaccines are the most effective and environmentally sound intervention for the control of tick infestations and pathogen infection and/or transmission [ 5 ].…”