Can you imagine the irony: a vampire whose bite makes you vegetarian?
Well, it’s real. A bite from the Lone Star tick has been known to make people allergic to alpha-gal, a component of red meat. You can’t make this stuff up, people!
The story of how this connection was discovered is similarly intriguing, diving now into the mystery genre.
In the mid 2000s, a promising new anti-cancer drug called cetuximab was speeding through its FDA trials. The only catch? A large cluster of side effects in patients living in the American Southeast.
It was known from the beginning of the trials that 3% or less of patients have adverse allergic reactions to the drug. Yet, in states like North Carolina and Tennessee, the numbers for this negative side effect hovered around 22%.
Why was this happening? The doctors at the pharmaceutical companies creating the medicine, Bristol-Myers Squibb and ImClone Systems, could not figure it out. Thomas Platts-Mills, lead doctor at University of Virginia’s Division of Allergy and Clinical Immunology, and his team were brought on the case.
Platts-Mills and team were able to develop a test and discovered that patients that had allergic reactions to the cetuximab trials had actually been allergic beforehand–they had heightened levels of antibodies that can identify and attack specific invading molecules, triggering an allergic response.
The coalition of doctors was able to show that these patients had particularly high levels of an antibody that binds to alpha-gal, a string of two sugars that was known to appear as biomarker in the tissue and blood of non-primate mammals. You can think of it as a different blood type.
Testing the cetuximab, the team discovered that it also had the alpha-gal biomarker attached to it. A smoking gun… but of what? Why did the cetuximab have this biomarker, and why were patients in the American southeast particularly sensitive to it?
The crucial clue came when the University of Virginia team compared a map of the incidences of cetuximab allergic reactions to a map of reported Rocky Mountain Spotted Fever (RMSF) cases. They matched well.
Though it has the Rockies in its name, Rocky Mountain Spotted Fever is most prevalent in southeastern U.S. states. RMSF has intense flu-like symptoms that are caused by infection with the bacteria Rickettsia rickettsii, a bacteria that lives in ticks such as the Lone Star tick.
The team began to suspect a connection. At this point, in 2008, Platts-Mills and two other team members themselves developed an allergy to red meat… and “each one distinctly remembered being bitten by ticks weeks or months prior to the development of symptoms,” they wrote in a wonderful article after the fact.
Perhaps, the team thought, the ticks somehow make their victims susceptible to alpha-gal, the biomarker found in both red meat and cetuximab. They scoured the literature and found one study from Australia that showed 25 patients in Sydney developing red meat allergies after being bit by ticks. Come, Watson, come: the game is afoot!
Going back, Platts-Mills and team (who I can only picture now munching sadly on some salad greens) asked all their patients that had strong allergic reactions to cetuximab if they recently had been bitten by any ticks. Sure enough, most of them said they had been.
It is now widely known in the allergy research community that bites from a few species of ticks (in the U.S., mostly the Lone Star tick) can trigger this alpha-gal hypersensitivity. How exactly this happens is still a mystery: is it something in the tick’s saliva? Does the previous batch of blood the tick sucked have an effect? Or is it some microorganism that causes this, just like a bacteria carried by ticks causes Lyme disease.
Hopefully the figure out, and soon… as the climate changes, warmer average temperatures allow ticks to expand their habitat, increasing the amount of people at risk of tick-borne illnesses.
Image credit: CDC