How does a tick bite cause a red meat allergy?

Cases of alpha-gal syndrome, a red meat allergy that comes from a tick bite, are climbing fast. But why does it only develop in certain people?

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:02Flora Lichtman?

  Hey, it's Flora and you're listening to Science Friday. For two decades, a perplexing illness has been spreading. After a Lone Star tick bite, people find themselves having a severe allergic reaction to red meat. Gone are the days of burgers and steaks. Some people are sensitive even to the smell of barbecue or cow-derived gelatin. This tick-borne allergy is called Alpha-Gal Syndrome. The CDC estimates up to 450,000 people in the US may be affected, and that's up from just a few dozen documented cases in 2009. Dr.

• 0:43Flora Lichtman?

  Scott Cummins started researching Alpha-Gal Syndrome almost 20 years ago, before anyone really knew what it was. He was part of the team that tied this allergy to ticks. He's an allergist and immunologist at the University of North Carolina's medical school. Scott, welcome to Science Friday. Thanks for being here.

• 1:01Speaker 01

  Thanks for having me.

• 1:03Flora Lichtman?

  I think people think of Alpha-Gal Syndrome as a red meat allergy. That's the shorthand. But what are the symptoms?

• 1:11Speaker 01

  Well, they're often the classic symptoms that bring people into an allergist's office, so itching, swelling, hives. And then frequently, there's accompanying gastrointestinal distress, so terrible abdominal cramping and pain, often nausea, vomiting, diarrhea. You can even have progression from there, where people will feel short of breath or have difficulty maintaining their blood pressure, the things that we think about as anaphylaxis.

• 1:46Flora Lichtman?

  What are people exactly becoming allergic to?

• 1:51Speaker 01

  Well, they're allergic to a sugar. So alpha-gal is a carbohydrate and the allergic antibody recognizes alpha-gal, which is present in the meat and tissues of all non-human mammals.

• 2:09Flora Lichtman?

  Okay, so this is a sugar that we must encounter all the time throughout our lives. So what is in the lone star tick that is making people sensitive to the sugar?

• 2:22Speaker 01

  Well, the ticks, it turns out, seem to have the sugar. And so when they bite a human, their tick saliva and factors in the tick spit seem to cause the human immune system to create this allergic response. And in some ways, alpha-gal is just sort of an innocent bystander. And if it weren't in hot dogs, hamburgers, et cetera, we probably would never even know about this allergy. But the distribution of alpha-gal in the foods that we eat and the medications that we take create that issue.

• 3:01Flora Lichtman?

  I mean, can we get into the nerdy details here, though? Why is my body suddenly recognizing this sugar as bad when it comes from a tick, but not when it comes from a hot dog I've had the day before?

• 3:11Speaker 01

  Yeah, it's a great question. And there's probably a nuanced answer, only some of which we really know about. But one portion of that is the route of administration. So oral, like you're eating your hot dog or hamburger, that seems to be associated with tolerance. So very unlikely to develop an allergic response just by consuming the food, particularly when it's been consumed for decades. The skin, however, is a fantastic way to make an allergic response. So it probably really matters that the tick bite is happening to our skin. And we don't really know the exact, like, factor and how it's hooked to

• 3:55Speaker 01

  alpha-gal, but probably the tick saliva contains what we might call alarmens. So it turns the human immune system on and activates it. And basically, it's like a danger signal to our immune system. And then alpha-gal just... Becomes an innocent bystander that we make an allergic response to.

• 4:18Flora Lichtman?

  Is an alarm in a technical term?

• 4:20Speaker 01

  It can be, but it's also a simple term.

• 4:25Flora Lichtman?

  You published a study recently that analyzed blood samples from people across 10 states. And you had this sort of amazing finding that one in four people had alpha-gal antibodies in their blood. What does this mean? Because not all those people have the syndrome, right?

• 4:44Speaker 01

  Correct, not at all. The numbers seem incredibly high, right? 20, 30% of blood donors in some states. But that's just what we call sensitization, meaning you have a positive blood test. Overwhelmingly, those people would eat red meat just fine. We have a major issue in the field of allergy and immunology with our blood test and our skin test for that matter, too. They are not good screening tests. They should be used when we suspect someone has an allergy. So just taking a lot of samples and applying the test is not how that test should be used.

• 5:28Flora Lichtman?

  Does that mean that those people who were positive for these antibodies were bitten by a lone star tick?

• 5:35Speaker 01

  Basically, we think that's the truth. In some ways, it probably is a marker for lone star tick bites and other bites, too, because alpha-gal syndrome is a global issue. So it happens beyond just lone star ticks. And you're correct to think that the alpha-gal IgE that we detected in this recent publication, that probably serves as a marker for tick bites.

• 6:01Flora Lichtman?

  What do you define IgE for us?

• 6:03Speaker 01

  It's just the allergic class of antibody. So if you're allergic to cats or dogs, your allergist, immunologist, might say you have IgE to cat or dog.

• 6:14Flora Lichtman?

  Okay, so this is probably the million dollar question, but why do some people develop the syndrome and some people don't?

• 6:21Speaker 01

  That is the million dollar question and we're not sure. So there's clearly some risk that is attributable to the tick. And there are, there are good studies that look at male ticks versus female ticks and what they've been fed on. And the, the scientists can detect different levels of alpha gout in the tick saliva between various life stages, between males and females. So it probably really matters exactly which tick you were bitten by. But then there's certainly going to be host issues too. As humans, we find often I will have a spouse or a partner in the exam room.

• 7:03Speaker 01

  And many times they'll say, well, you know, as long as I go out with Debbie, I don't get any tick bites. They all go to her. And so there's, seems to be very clear risk things, risk factors that are happening at the host level. The other example is blood type. It is becoming increasingly clear that if you're blood type B or AB, your risk of developing alpha gout syndrome is much lower than people who are A or O. So your question is, is right on. These are the things that we're thinking about too. I think there's a tick risk and a host risk, and we're still working on both of those.

• 7:43Flora Lichtman?

  What's the profile of the tick that's most dangerous? So I know which ones to avoid.

• 7:47Speaker 01

  The female lone star tick is a bad actor. But I will tell you that increasingly we hear a lot about the larval life stage, which some people call seed ticks. They're really difficult to see. They're like the head of a pin and you can be bitten by hundreds at once because they often are, come out of a egg mass. So there's thousands of these tiny little ticks that are laid in a very small space. And if you brush by the wrong leaf or blade of grass, you can literally end up with hundreds of bites and that also seems to be a bad actor.

• 8:24Flora Lichtman?

  I remember this happened to me as a kid growing up in Missouri. And I just remember my leg being covered and brushing them off like it was, I'll never forget. Anyway, side note, why is the allergic reaction delayed? Like if people with peanut allergies, you see it right away, right? They can swell up within minutes. This takes hours. Why?

• 8:46Speaker 01

  We think it has to do with the fat content of the meat or meal being the important part of delivering alpha-gal. So fat has alpha-gal on it and it can exist in the science realm as what we call a glycolipid. So a fat molecule that has sugar on it. It turns out that the absorption of fat takes much longer than proteins or carbohydrates on their own. That whole process takes several hours. And patients will often say that the fattier meals bother them more. If you were to give alpha-gal intravenously, as was occurring with the cancer medicine, cetuximab,

• 9:31Speaker 01

  those reactions happen within minutes.

• 9:36Flora Lichtman?

  There's been a lot of attention on alpha-gal in Martha's Vineyard and Long Island. How widespread is it and where is the highest exposure?

• 9:46Speaker 01

  Well, it is fairly widespread. So basically, the entire East Coast, all the way west to around the Rockies, because we're starting to see a lot of cases in Oklahoma, Nebraska. There are cases around the Great Lakes areas as well. And I mentioned Maine, so we're we've extended now from the original sort of southeastern states up the East Coast. And then there are these hotspots. Suffolk County, Long Island, has a tremendous issue with AGS. So as you mentioned, Martha's Vineyard seems to be a recent hotspot and is currently receiving a lot of attention because the rates have just gone up exponentially.

• 10:30Flora Lichtman?

  We have to take a quick break, but when we come back, we'll talk about whether new treatments or interventions are on the horizon. Stay with us.

• 10:42Speaker 02

  Support for Science Friday comes from the Hysing Simons Foundation, unlocking knowledge, opportunity, and possibilities. More at hsfoundation.org.

• 10:57Flora Lichtman?

  Okay, are there treatments? I know that Zolair is an allergy medicine that seems to work, but is it an approved treatment? Is it an off-label use?

• 11:07Speaker 01

  No, Zolair is on-label because Zolair, as the FDA approved it, is for any IgE-mediated food allergy. So there's the IgE term again. But AGS falls in that too. Same as peanut, cow's milk, egg, et cetera. So you can use Zolair broadly, and it's on-label for alpha-gal syndrome. We have a host of patients on it, probably nearly 100 at this point, and they do quite well.

• 11:38Flora Lichtman?

  Do they take it after a possible exposure? Or are you on it all the time?

• 11:44Speaker 01

  You are on it all the time. So the way it works is it binds IgE. And over a period of months, generally, basically kind of renders you non-allergic. So a small exposure, cross-contamination, that kind of thing doesn't cause a reaction.

• 12:01Flora Lichtman?

  I mean, for other allergens, we've talked about, you know, early and often exposures. Is there a version of that that people are thinking about for alpha-gal syndrome?

• 12:13Speaker 01

  Well, we'd love to have that. Something like what we call oral immunotherapy, or OIT for short, where you basically eat a tiny bit of the allergen every day to sort of desensitize yourself. I think that's possible in the long term with alpha-gal syndrome. But we really struggle at the moment with what that should be. I don't think we should, at least based on the dietary guidelines that we're being told, the cardiovascular risk with red meat. I don't know that we should be feeding our patients or telling them every day, you have to eat a certain amount of beef. I worry that in the long run, the cardiologist is going to come back to me and say, you did what?

• 12:57Speaker 01

  But I think it's doable. We just got to figure out the form of alpha-gal for that daily consumption.

• 13:05Flora Lichtman?

  What about vaccines?

• 13:07Speaker 01

  Yeah, we are thinking about vaccines. We need to know what that factor or factors are in tick saliva that really could drive the immune response. And I think, once we know that, we can take an approach similar to what we do for, say, bee or wasp venom, where you can't prevent that first bad bee sting reaction, but then we put them on venom shots and then future stings don't cause that allergic response. So I think we could do that for the tick bite. We just have to know what it is in the tick saliva that's the real trigger.

• 13:47Flora Lichtman?

  You see patients, I'm sure, across the allergy spectrum. What is this diagnosis like for people? Is it emotionally different from getting a different kind of food allergy diagnosis?

• 14:00Speaker 01

  It seems to be emotionally different. And I think part of that is most patients that I'm seeing these days, because I'm in the adult clinic, they're either adolescents or adults. So they've safely eaten beef, pork, lamb, venison, et cetera, for years. And then you take that away. For some people, it's a big part of their diet. And the other thing I tell folks is when you're an adult, we don't get together for a playdate. We get together for lunch, or coffee, or dinner. So there's a social part of this, too, that really changes for people. And we're, I think, increasingly aware that there is a mental health aspect to these severe food allergies.

• 14:44Flora Lichtman?

  Working on this for 20 years, has it changed your feelings about ticks or your behaviors?

• 14:49Speaker 01

  Oh, yeah, absolutely.

• 14:52Speaker 01

  Now, if I'm going to be out there, I'm definitely using permethrin. And I'm not bashful about tucking my pants into my socks and, you know, using some double sided tape where I need to. I think what we learned over time is that Truly an ounce of prevention on the tick bite side can save you years of this severe allergic reaction.

• 15:16Flora Lichtman?

  I mean, this has been basically your career. What do you still want to know?

• 15:22Speaker 01

  We have Zolair. We'd love to have a more targeted treatment. And, and I think we can make some breakthroughs there. I'd love to have an on-demand treatment in some way because the, the allergy actually tends to go away over time. The, the immune response that the tick bites tend to trigger does not seem to be a permanent one. So this thing can fade over time. The issue is additional tick bites basically boost that allergic response. So something that should go away in three to four years with no additional tick bites

• 16:02Speaker 01

  can take decades to go away or perhaps never resolve if someone has to work outside or gets additional tick bites. So I would love to have a therapy that we could use very quickly in someone who already has the allergy and we could deliver a therapy on demand after a tick bite to try to intervene and prevent that rise or boost in the allergic response.

• 16:29Flora Lichtman?

  Are we anywhere near that? Is that pie in the sky or are you working on that?

• 16:34Speaker 01

  No, I think there are some candidate molecules that are available and, and hopefully we can try to do some, some clinical trials. We're, we're really focused in that area. I think the other thing is, as we mentioned earlier, trying to understand the risk that the tick poses, but then also understand what the risk factors in the host side might be. And if, if any of those are potentially modifiable, then that would be something that, that would potentially offer a treatment or, or therapy as well.

• 17:05Flora Lichtman?

  It's interesting to hear you say that because I think people who feel like they're a magnet for insects will feel very validated by this.

• 17:14Speaker 01

  When you talk to patients, you, this theme comes up over and over again, that somehow you're in the woods with your friend or spouse, partner, and one of them is more of a, a tick magnet or bug magnet. It comes up. All the time. And so I really think there is something to that.

• 17:32Flora Lichtman?

  There's something real there. Thank you, Scott.

• 17:35Speaker 01

  Thank you.

• 17:36Flora Lichtman?

  Dr. Scott Cummins, Associate Chief for Allergy and Immunology at UNC School of Medicine in Chapel Hill, North Carolina. This podcast was produced by Kathleen Davis. And if you're itching for more from us, check out our newsletter, sciencefriday.com/newsletters. Thanks for listening. I'm Flora Lichtman.