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The Meat Allergy

A History

The alpha-gal story: Lessons learned from connecting the dots‘ was released on November 21, 2014, a story chronicling how a series of anomalous medical cases led to the realisation that thousands of people from all over the world had developed serious, if not life-threatening, allergies to meat from the bite of a tick.

Beginning in 2004, two biomedical groups were testing the effects of a mouse-derived cancer growth inhibitor called “cetuximab” on groups of American patients. Within a year, the groups noted that some of the patients were reacting hypersensitively after being given the infusion for reasons unknown. In a rare few cases, the individuals in the trial experienced reactions so severe they proved fatal.

Between 2006 and 2008, the three authors of ‘The alpha-gal story’ evaluated patients who had previously presented with urticaria (hives), angioedema (swelling beneath the upper layers of skin), or anaphylaxis (a severe and generalised allergic reaction involving the respiratory system and/or cardiovascular system) symptoms in response to cetuximab infusions. Based on several patient suggestions, the authors investigated and confirmed that the immune systems of these patients had developed an allergic sensitivity to red meat products within their bloodstreams.

Reported cases pointing the finger at tick bites as the cause of meat allergies first pop up around the year 2000 but it took until 2010 to paint a full picture of the disease and its geographical cross-overs.

Lone Start Tick

The distribution of the lone star tick was found to coincide with geographical occurrences of allergic reactions to red meat consumption in the US. Image attribution: user Benjamin Smith

By 2008, ‘The alpha-gal story’ authors Steinke, Platts-Mills, and Commins had come across an eyebrow-raising pattern. Of all the analysed American cases of allergic reactions to the cetuximab treatment, they were 10x more likely to occur in southeastern states. The same area also happened to line up with occurrences of Rocky Mountain spotted fever, a bacterial disease carried by the lone star tick.

In a teasing twist of fate, Platts-Mills himself and two other members of the research team then came down with the allergy during this same period. Each of them remembered being bitten by a tick.

By 2009, the tick-allergy connection was steadily creeping into reports on the paralysis coming out of Australia by 2013 European scientific streams added two more tick species to the collection.

And yet, a look into unreported documents suggests a slightly different story. Intrigue into reactions to red meat actually started in 1989. Two Georgian researchers, Mrs Sandra Latimer and Dr Antony Deutsch, noted 10 cases of people who exhibited hives or anaphylaxis after consuming mammalian meat. The two even referenced tick bites received by each subject some weeks if not months before the first onset of symptoms before audiences including the Georgia Allergy Society and US Centres for Disease Control in 1991.

But regardless of who discovered what first, by the late 2000s ticks were widely accepted as the origin of the meat allergy. With the cause isolated, attentions then turned to its mechanisms.

The Meat Allergy Diagram (Simplified Version #2)

Allergic reactions to mammalian meat develop from a single tick bite. The bite primes the body’s immune system into overreacting to the presence of alpha-gal in the meat. Image attributions: Tick – user Benjamin Smith; Mast Cells – user Ed Uthman; Urticaria – user Bruce Blaus.

The Mechanisms

Red meats host a small assortment of sugars hitched on to the end of their proteins. One of them, found exclusively in mammals, is galactose-alpha-1,3-galactose. For sanity’s sake, this gets shortened to “alpha-gal”.

As it happens, the bite from a tick appears to stimulate the development of allergies specific to alpha-gal – that is, specific to mammalian meat.

Once that sensitivity has been developed, allergic reactions manifest once the alpha-gal appears in the circulation. Unlike most allergies which often take 20 minutes or less to reach peak symptoms, that delay for alpha-gal to enter the bloodstream can take 2-6 hours, a delay which partially explains why identifying the symptoms’ causes took so long for early researchers.

For those in the Western world, beef, lamb, pork, and occasionally even dairy are the main items struck from the menu. Poultry and seafood remain greenlit, and if primate ever happens to be an option that too stays in the clear. And whilst the end of steak nights may seem to be reason enough to fear the presence of the tick, the allergy puts forwards a number of quite serious problems.

Take antivenoms for instance. Antivenoms are produced by injecting safe amounts of venom into a third party, typically an unsuspecting horse, to grow venom immunity. The plasma, containing venom-immune white blood cells, gets removed and refined before being frozen for later injection. In Australia – a.k.a. Venomville – paralysis ticks are found up and down the east coast alongside a cocktail of dangerous critters on land and in the ocean. They also happen to be one of the foremost meat allergy transmitters. Seeing as though any antivenom will be lined with alpha-gal from a horse, Australians who contract the meat allergy are forced into a dangerous predicament if they every need antivenom administrated.

A similar issue was at the heart of why those unfortunate cancer patients suffered allergic reactions to their cetuximab treatments. It turns out the mice used to generate cetuximab left alpha-gal littered through the infusion, triggering their predisposed over-sensitivity to it and leaving them suffering from a varying selection of allergy symptoms.

tick map

The Known Unknown

The missing link in our understanding lies between the stages of being bitten and of developing an alpha-gal sensitive IgE response – between the bite and getting an over-reactive allergic reaction. In trying to fill this gap, researchers have been left with three theories explaining how a tiny arachnid can spoil BBQs at points all over the globe:

  1. something in the saliva of the ticks induces an allergic response to the alpha-gal sugar present in mammalian meat;
  2. the immune system initially reacts to the alpha-gal sugars left over from a previous meal of the tick. When we are then bitten that blood gets into our bloodstream and we develop the recurring allergy from it;
  3. a third party using the ticks as hosts (probably a bacterial species in this case) induces the allergic response when we are bitten by the tick.

A Growing Concern

At least six species of ticks across Australia, the United States, Europe, parts of Asia, and Africa have now been identified as vectors for the allergy’s distribution. Amblyomma americanum (the lone star tick) in the US and the Ixodes holocyclus (the paralysis tick) in Australia are the more prolific offenders, both having been directly shown to instigate serious allergic reactions. With the increasing availability of warmer environments and small to moderate mammals, the two species also now seem to be consistently expanding their ranges into populated areas.

Seeing as though EpiPens remain the front, and only, line of defence against the allergy, it’s fair to say that the issue is rather under-understood. Even with preliminary breakthroughs in suppressing over-sensitive allergic reactions like that seen earlier this week, they remain just that – preliminary. For the meantime, it seems meat allergy sufferers are left with little else than strict dieting and visits to the emergency room until anything resembling a cure presents itself.

 

Further Reading:

The alpha-gal story: Lessons learned from connecting the dots‘ – Steinke, Platts-Mills, Commins; The Journal of  Allergy and Clinical Immunology

Oh, Lovely: The Tick That Gives People Meat Allergies is Spreading‘ – Megan Molteni; WIRED Magazine