Red meat allergies and ticks
Via Twitter, Heather’s friend Parva pointed out this story in the Wall Street Journal which describes a set of case studies of individuals who showed mild to severe allergies after eating various types of red meats such as beef, pork, or lamb. Epidemiological research at the University of Virginia Medical Center found that many of these patients had reported tick bites previously, and blood analysis indicated that the patients also had IgE antibodies (the kind associated with allergies) which were directed at antigens found in animal meats. In the WSJ summary, the basis of the syndrome appears to be either the direct transmission of animal antigens from a previous meal into a human via the tick intermediate, however the researchers could not exclude the possibility of either an infectious agent such as a bacterium that causes the syndrome after transmission by a bite, or a sensitivity to tick saliva creating the allergy condition.
In trying to find out more about the mechanism of this finding, I located this article from the primary medical literature from the researchers which reported their initial findings in 2009. In this article, it was found that IgE antibodies in the patients were directed at a carbohydrate antigen galactose-α-1,3-galactose (alpha-gal), which is commonly found on the surface of proteins from many non-primate mammals. Most non-immunocompromised adults already make significant numbers of antibodies to these antigens, but of the IgG subtype, and approximately 1% of the antibody present at any given time is directed against α-gal in the blood of a healthy adult. It is this IgG antibody against α-gal that is responsible for the extremely rapid response of pig-to-primate tissue rejection.
As can be seen from the figure, patients reporting the red meat allergies demonstrated strongly positive responses against a variety of meat antigens in a skin prick test, however it was noted that the responses were much more robust against freshly prepared antigen as opposed to commercially available antigen extracts that are generally available to allergists. The researchers could find no correlation between any of their patients and any potential foodborne insult or a genetic predisposition to developing the responsible IgE antibody.
Two intriguing questions were posed by the study. First, unlike many other allergy hypersensitivities, the reactions observed due to red meat ingestion developed over the course of hours instead of minutes. The authors suggest that possibly it is essential for the animal antigens must be partially digested before they can produce a more severe result. Second, the initial trigger that causes the immune system to produce the allergy-associated IgE antibodies instead of the usual IgG antibodies remains unknown. Further analysis was suggested as a result.
One possible explanation to the latter question was put forth in a publication from 2013. In this study, it was noted that there is a structural relationship between the α-gal antigen from animals, and the carbohydrate antigen found on human B-group red blood cells. Individuals who have type B blood do not make any antibodies against their own blood; if they did, they would experience cytolytic rejection of their own blood cells, which would have terrible effects. The researchers found that individuals of blood group B made significantly lower levels of antibody against the animal meat antigen. With this observation, one would then be able to predict that in a non type-B individual that they might show elevated levels of antibody against both the B blood antigen and the α-gal antigen. This was not the case, however, as in the allergy patients only antibodies against the animal antigen were found, with no measurable antibody against the human blood group antigen. They did find though that in patients with an elevated IgE (allergic) response that an elevated IgG (normal) response was also seen. They conclude from this analysis that all humans on a meat containing diet will produce normal antibodies against the meat antigens. In certain individuals–and blood group appears to offer some measure of protection–introduction of these antigens via an abnormal route by tick bite or other means causes an additional immune response to occur with the allergy associated symptoms.