Whether you or someone you know has suffered from them, many will undoubtedly recognize the puffy, watery eyes, scratchy throat, hives, and difficulty breathing that are often triggered during an allergic reaction. The irritants that cause most allergies are generally quickly identifiable, as responses to them are generated rapidly after exposure. However, some allergic reactions can come on seemingly unannounced, without any clear basis. These inexplicable anaphylactic events are known as “idiopathic anaphylaxis,” or IA. Although IA often passes without a known cause, doctors and scientists are beginning to discover that some cases may actually be the result of sensitivity reactions developed against  red meat, as several reported cases have occured 3-6 hours following its ingestion. More surprising is the alleged source of these reactions, which are thought to develop following bites from Amblyomma americanum, or the Lone Star tick. Although the exact mechanism through which red meat allergies are conferred from ticks to patients is not well understood, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) have determined that when patients present with IA, they should be screened for red meat allergies, particularly when they live in an area inhabited by the Lone Star tick and have a history of tick bites.

What does it mean to have a red meat allergy?

Allergic reactions are driven by the activation of  mast cells, which are a type of immune cell that can be found in multiple tissues throughout the body. Mast cell activation is mediated through antibodies. Antibodies are Y-shaped proteins found in the blood that bind specifically to particles known to generate immune responses, called antigens. Multiple types of antibodies, or “immunoglobulins,” exist in the body and perform a variety of functions to protect you from different potential threats, such as bacteria and viruses One specific type of antibody, known as “immunoglobulin E” (IgE) plays a critical role in both allergic reactions and responses to parasites. For an allergic reaction to occur, one end of an IgE molecule must first bind to a mast cell (Figure 1). The Y-shaped end of the IgE molecule will then bind to allergy-causing antigens in a patient’s blood serum, which causes the mast cell to become activated. Once activated, mast cells release multiple chemicals including histamine and tryptase, which act as signals for your body to defend itself and fight off or remove offending antigens. These signals result in inflammation and the subsequent hives, watery eyes, and scratchy throat one often associates with allergic reactions.

Consequently, when someone has an allergy, you can expect to find IgE molecules that specifically recognize and bind to the allergy-causing antigen in the person’s blood. To this end, Carter  et al. examined 70 patients who suffered from IA to determine if their episodes could be explained by sensitivity to red meat. By examining serum samples, the team determined that 6 of the IA patients within the cohort had IgE antibodies specific for the sugar galactose-α-1,3-galactose (α-gal) at levels above what is considered “normal.” The sugar α-gal is found only in the meat of non-primate mammals, including pork and beef. All 6 patients had consumed red meat several hours prior to the start of their anaphylactic episodes. In addition, all 6 patients were found to have non-B blood types. This is consistent with other reports of α-gal allergies and is thought to be due to structural similarities between α-gal and B-type blood. However, the group did go on to explain that, while what they found follows trends seen with α-gal sensitivity, blood type is not necessarily indicative of whether someone will be sensitive to a specific allergen. Interestingly, the group found that when the α-gal patients were put on diets to avoid red meat consumption, they did not suffer from any more anaphylactic episodes, further confirming that their initial IA episodes were the result of the sudden development of sensitivities to red meat.

How do red meat allergies develop?

Curiously enough, the group found that all 6 men had a history of tick bites, and lived in regions where the Lone Star tick is known to reside. Previous epidemiological studies have determined that the Lone Star tick is likely the causative agent of α-gal sensitivities. These studies found that patients with IgE antibodies against α-gal live in regions where Lone Star ticks are common, and that these antibody responses correlate with a history of these tick bites. Furthermore, it was determined that there was a correlation between the presence of antibodies against  α-gal and antibodies against tick proteins. Scientists are actively working to generate a mouse model to definitively conclude whether these bites are truly the cause of α-gal sensitivities and red meat allergies. However, for the time being, the work presented by Carter et al. has further served to bolster the link between these otherwise inexplicable red meat allergies and Lone Star tick bites.

Although a link has been made between tick bites and red meat allergies, exactly how this sensitivity is conferred is not well-understood. While it has been shown that tick saliva can drive very strong immune responses and lead to high levels of total IgE antibodies in the blood, exactly what drives the presence of IgE against  α-gal has not been explicitly defined. Furthermore, the delay between the ingestion of red meat and the onset of anaphylactic reactions to α-gal has made it exceedingly difficult to pinpoint and further study these processes. As such, the group concluded that when cases of IA present in regions inhabited by Lone Star ticks, α-gal allergies should be tested for, as they could provide both a simple solution to avoid future anaphylactic episodes as well as an opportunity to gain more insight into the link between tick bites and red meat sensitivity.