Uncovering the meat-allergy mystery with ticks

By Linya Thng 

Understanding the immunological basis of allergies remains a big question within the immunology community, especially when it comes to understanding the unique allergy towards mammalian meat. These allergies can be triggered by some of the unlikeliest creatures on the planet; one that most wouldn’t cross even the most accomplished minds in immunology is ticks. These minuscule insects are present in almost every country in the northern hemisphere and measure only a few millimeters in length; scarcely noticeable to the naked eye. It is their small-scale that makes humans often oblivious to their presence and dangerous if they put human lives at risk.

Red meat/ alpha-gal allergy

The recurrent episodes of the life-threatening allergy reactions are also known as anaphylaxis. Anaphylaxis consists of a wide spectrum of symptoms including the dropping of blood pressure to critical levels and the constriction of airways. This severe allergic reaction is hence characterized as fatal and requires a long-term risk assessment (Kuehn, 2018). The first case of this mysterious allergy was reported in June 2001. Peter Moore, a local teacher from the coastal suburb of Australia, Sydney, was a victim of this rare mammalian-meat allergy. After the consumption of pork spareribs, he retired to bed, only to be awoken with signs of breathing struggles and his torso filled with massive red welts (Steinke, Platts-Mills & Commins, 2015). Several similar cases of the unusual misdiagnosed allergy were reported since. 

A high proportion of patients were mistakenly diagnosed as unexplained anaphylaxis. The nature of anaphylaxis diverges from the common allergies and routine allergy tests are generally unable to detect the antibodies for alpha-gal (Carter et al., 2018). The abnormally prolonged time gap between a meal and the appearance of the first symptoms is one of the contributing factors to the misdiagnosis of alpha-gal allergies. In general, common food allergens tend to appear approximately 5-30 minutes after exposure. In comparison to the typical reactions, alpha-gal allergy tends to occur only after 3-6 hours after the consumption of red meat – this makes it harder to detect the causative agent of the reaction (Hamsten et al., 2013).

Characterization of Amblyomma americanum, Lone Star Ticks

Ticks are generally cunning parasites and are characterized for its necessity to remain attached to its host for a prolonged period in comparison to other blood-sucking arthropods. To do so, ticks manipulate their hosts’ defenses in order to remain unrecognized. The manipulation is heavily dependent on their saliva, which consists of a mixture of chemical components, including immunosuppressants, immunomodulators, anesthetics and anticoagulants (Steinke, Platts-Mills & Commins, 2015). What distinguishes and varies between the species is sialome – the proteins expressed in the salivary glands of these blood-sucking arthropods. The peculiar case of ticks being the causative agent of this rare allergy puzzles many within the Immunology field. Ticks are usually seen as main carriers of infectious diseases including Lyme disease, Rocky Mountain Spotted Fever (RMSF), and many others (Kuehn, 2018). In this article, the focus lies on Amblyomma americanum, commonly known as the lone star tick, which are linked with the development of alpha-gal allergy. The distribution of lone star ticks ranges from Southeast through the Eastern United States. Researchers at NIAID uncovered an association between these rare cases of anaphylaxis and tick bites, specifically Lone Star ticks (Carter et al., 2018). Bites from Lone Star ticks in either the larval or adult stage are heavily linked to the development of red meat allergy. 

National Institute of Allergy and Infectious Diseases (NIAID) identified the key molecule naturally found in red meat, solely responsible for the causation of such rare allergies (carter et al., 2018). Clinical trials and further analysis revealed that alpha-gal allergy is associated with a specific sugar found on red meats, called galactose-α-1,3-galactose, or alpha-gal (α-gal). Alpha-gal is commonly produced in a multitude of mammals, excluding humans and some primates. The synthesis of alpha-gal involves a specific gene which encodes for alpha-1,3-galactosyltransferase (Steinke, Platts-Mills & Commins, 2015). Due to the absence of this gene and alpha-gal in humans, this allows the production of novel IgE antibodies targeting the mammalian oligosaccharide. Studies demonstrated a large proportion of IgE antibodies were found in the southeastern United States (Hamsten et al., 2018).

Future Perspectives

Food allergies remain to pose a threat in the healthcare system and continue to generate urgency for research. The exact IgE response to the tick bites still remains ambiguous. The possibilities of external factors contributing to this immune response remain, such as the involvement of other symbiotic organisms. The explanation behind the symptoms of this mammalian red meat allergy also remains unanswered. Presently, the best theory for the delayed food response revolves around the absorption of lipid particles, but many loopholes stand. These unanswered questions serve massive potential for the enhancement of allergy management strategies.

References 

Carter, M. C., Ruiz-Esteves, K., Workman, L., Lieberman, P., Platts-Mills, T. & Metcalfe, D. D. (2018) Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis. Allergy (Copenhagen). 73 (5), 1131-1134. Available from: doi: 10.1111/all.13366.

Hamsten, C., Starkhammar, M., Tran, T. A. T., Johansson, M., Bengtsson, U., Ahlén, G., Sällberg, M., Grönlund, H. & Hage, M. (2013) Identification of galactose‐α‐1,3‐galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy (Copenhagen). 68 (4), 549-552. Available from: doi: 10.1111/all.12128.

Kuehn, B. M. (2018) Tick Bite Linked to Red Meat Allergy. JAMA : The Journal of the American Medical Association. 319 (4), 332. Available from: doi: 10.1001/jama.2017.20802.Steinke, J. W., Platts-Mills, T. & Commins, S. P. (2015) The alpha-gal story: Lessons learned from connecting the dots. Journal of Allergy and Clinical Immunology. 135 (3), 589-596. Available from: doi: 10.1016/j.jaci.2014.12.1947.