Kristina Carlson hadn’t paid much attention to the tick she removed from her torso while hiking in the mountains of North Carolina, United States, in September 2020. But a month later, back home in Mississippi, she told her doctor. joint pain and a bloated feeling in the stomach. The doctor had ruled out that she could be rheumatoid arthritis and a blood test revealed nothing definitive. Then she Carlson started having eye infections. In February 2021 she suddenly found a strange rash on her face; an emergency room doctor treated her as if she were shingles, but the rash did not improve.
When she returned to her doctor’s office, a nurse asked her, “Do you remember being bitten by a tick?” This led to another blood test that revealed antibodies associated with alpha-gal, a sugar found in the meat and fat of non-primate mammals.
Alpha-gal syndrome (AGS) is an allergic reaction that can arise after a lone star tick bite [Amblyomma americanum, chiamata anche zecca del tacchino, NdT]. Named for the white spot visible on the backs of adult females, these ticks are historically located in the south-central and southeastern United States and transmit the alpha-gal molecule from the blood of mammals they ate to people who sting later.
This is why anaphylactic shock is rapid and violent
Ticks have now been found in New Jersey and Long Island, New York State, with sporadic reports further north along the east coast and in parts of the Midwestern United States. The spread is prompting researchers to consider the potential long-term complications of AGS and further investigate the cause of the allergy using genetically modified meat.
Normally, when a person eats meat from non-primate mammals, such as cows and pigs, his body does not react to alpha-gal. But when a tick bite introduces the molecule, the immune system recognizes it as an invader and produces specialized antibodies against it known as immunoglobulin E (IgE). IgE antibodies bind to disease-fighting immune cells: white blood cells called basophils in the bloodstream and mast cells in tissues. The next time these cells come into contact with alpha-gal of any origin, including meat, the antibodies recognize it and the immune system attacks it.
The formation of IgE “can be thought of as the loading of the gun,” says Scott Commins, co-director of the division for allergies and immunology at the University of North Carolina School of Medicine and senior researcher at AGS. “By eating mammalian meat you then pull the trigger.”
The resulting allergic reactions, which typically begin two to six hours after alpha-gal ingestion, vary from person to person. They can be mild like a tingling in the mouth or extreme like anaphylactic shock. Some people with AGS can eat a double Cheeseburger and feel only a slight itch in the palms of the hands or a scattered hives. Other people who consume refried beans with a trace of pork fat may experience acute anaphylaxis. After eating meat, Carlson immediately felt tingling and sometimes mouth ulcers. Within 24 hours, he often suffered from eye irritation, joint inflammation, rashes on different parts of the body and swelling in his left arm.
There is currently no treatment or antidote for AGS itself. Epinephrine is the first-line treatment for anaphylaxis, and some other allergic reactions can be managed with medications, including antihistamines and corticosteroids. People with this syndrome need to do their best to avoid trigger foods. Eliminating mammalian meat and other products generally eliminates symptoms. “I eliminated all animal products,” says Carlson, “and the rash, infection, joint pain and inflammation disappeared.”
One consolation for Carlson and most of the other 34,000 Americans diagnosed with AGS is that the sensitivity to meat does not appear to be permanent and often resolves in four to five years. This is because the cells of the immune system that create the IgE response are immature B lymphocytes called plasmablasts. According to Commins, these cells do not appear to convert into long-term immunological memory cells, which remain on guard throughout life, as does immunological memory cells activated by some vaccines, which defend us from invaders for decades.
However, people who spend a lot of time outdoors, such as park rangers or land surveyors, may experience repeated tick bites. “These patients appear to develop long-lasting memory cells,” Commins points out. “Unfortunately, for them, the alpha-gal allergy is probably permanent.”
As the prevalence of lone star ticks increases, however, cases of AGS are expected to rise. “Ticks appear to be spreading,” says Richard S. Ostfeld, disease ecologist and scientist senior of the Cary Institute of Ecosystem Studies. “Unfortunately, the United States doesn’t have any kind of active tick surveillance program nationwide.” Sporadic records suggest the range of lone star ticks is expanding, Ostfeld says, “but we lack rigorous, high-quality data on where they are and how fast they are moving.”
The molecular mechanism of anaphylactic shock
The reason for their spread is also difficult to determine. The main hypothesis concerns climate change, but researchers hesitate to draw this conclusion because it is difficult to verify rigorously. “There are studies that suggest that as temperatures continue to rise, the geographic range of the lone tick will not expand,” Ostfeld explains, “while most studies indicate it will.”
What is clear is that climate change is lengthening the active season for at least some ticks, increasing the overall chance that people will come across these arachnids. As for black-legged ticks (Ixodes scapularis) in New York State, Ostfeld points out, “we have shown that both the larval and the nymphal stages appeared earlier and earlier as the climate warmed. To the extent that lone star ticks behave similarly, one would expect that their active season lengthens “.
Lone star ticks are less than three millimeters long and are very aggressive. They are often found in large groups and are able to sense the heat and carbon dioxide emitted by humans a couple of meters away. Then “they hunt you down”, adds Ostfeld. “They run to meet you.”
Researchers would like to find out whether IgE elicited by alpha-gal may contribute to or exacerbate other conditions. In a small 2018 study, Commins and his colleagues associated the antibody with unstable plaques in coronary arteries. In a larger study from 2022, in which Commins did not participate, researchers associated heart attacks with a positive blood test for alpha-gal allergy. “We are trying to understand if this immune response to alpha-gal is part of the bigger picture,” says Commins.
Commins is also in contact with a United Therapeutics biotech subsidiary, Revivicor, which raises pigs to provide organs for transplantation to humans. Animals are genetically engineered to be free of alpha-gal, because this sugar causes the human body to reject pork organs. In 2020, the US Food and Drug Administration approved the meat from these “GalSafe” pigs for consumption. In recent months, Revivicor has been shipping the meat to people with allergies and is considering selling the meat by mail order.
Commins would like to test people who eat GalSafe pork. If the alpha-gal molecule has been eliminated but people continue to react to the meat, researchers should reconsider the apparent cause of the AGS. “We’re sure it’s alpha-gal,” Commins concludes, “but I think that would prove it.”
(The original of this article was published in “Scientific American” on May 23, 2023. Translation and editing by “Le Scienze”. Reproduction authorized, all rights reserved.)
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