The alpha-gal syndrome: Understanding the role of tick bites, and the delays in severe anaphylaxis

The presence of serum immunoglobulin E (IgE) antibodies to the oligosaccharide galactose-alpha-1,3-galactose (α-gal) was first recognized during the investigation of allergic reactions to the monoclonal antibody cetuximab. The availability of an assay for IgE to α-gal made it possible to show that the patients who reported delayed allergic reactions to meat also had IgE to α-gal. This syndrome of delayed reactions to meat in patients with IgE to an oligosaccharide that was present in nonprimate mammals represented a complete contrast to the other forms of food allergy. However, the realization that the sensitization resulted from bites of the lone star tick, Ambloymma americanum, provided an explanation for the increase in cases in an area of the United States where there had been a major increase in the deer population, which is the primary breeding host of this tick. In contrast to almost all other IgE-mediated reactions, there is no relationship between the delay after eating red meat and the severity of allergic reactions. There is also increasing evidence that serum tryptase in the range of 20-90 ng/mL can occur after severe reactions related to α-gal. In addition, a recently reported fatal anaphylaxis, which started 4 hours after the individual ate a hamburger, included a postmortem tryptase of >2000 ng/mL. A working hypothesis to explain the delay in reactions relates to the time taken to process glycolipids in food derived from mammals, first into chylomicrons and, finally, to low-density lipoproteins. However, the quantitative presence of α-gal that remains on these particles may have major individual differences. In contrast to the patients who have symptoms related to eating meat, there are many individuals who are sensitized and who are not aware of any symptoms. In addition, individuals who are sensitized to alpha-gal can react rapidly to intravenous injections to the monoclonal antibody cetuximab, or polyclonal antibodies to venom, or the newer antivenom digested to Fab or Fab'2.