Episode transcript
Time stamps
1:04: General overview of food allergen components
5:05: Discussion on milk allergen components
7:07: Discussion on egg allergen components
9:45: Molecular components found in peanut, tree nut, and seed allergens
13:22: Discussion on peanut allergen components
15:54: Landon’s story and the impact of allergen component testing
21:13: Discussion on tree nut allergen components
24:28: Importance of precise diagnosis and management
Announcer:
ImmunoCAST is brought to you by Thermo Fisher Scientific creators of ImmunoCAP™ Specific IgE Diagnostics and Phadia™ Laboratory Systems.
Gary Falcetano:
I'm Gary Falcetano, a licensed PA with over 11 years-experience in allergy and immunology.
Luke Lemons:
And I'm Luke Lemons with over five years of experience writing for healthcare providers and educating on allergies. You're listening to ImmunoCAST, your source for medically and scientifically backed allergy insights. Today on ImmunoCAST, we're going to be talking about food allergen components. In the past, we've talked about pet allergen components and we've referenced food allergen components numerous times in past episodes. So really excited to have a full episode dedicated to speaking about them today.
Gary Falcetano:
And as a reminder, Luke, these are serological IgE tests that are utilized by primary care providers, pediatricians, allergists alike.
Luke Lemons:
Yeah. And again, they add such incredible value to understanding a patient's potential allergy. And especially when it comes to food allergy, these components are very helpful.
Gary Falcetano:
And as you mentioned, we've talked about other types of components. We've mentioned food allergen components in the past, but this is really where it all started. So I mean, the first food allergen components that were introduced for clinical utilization in the U.S. were actually milk and egg components, which we'll talk about in a minute. And then we've had a series of other food allergen components introduced since then, but they've been around now since actually the mid-2000s.
Luke Lemons:
Yeah, and I think we should... Before we dive in, because we have a great episode today about milk and egg, about peanut and tree nut and even seeds and the components that are involved within them. I think we should take a step back and just do a quick refresher for maybe those who haven't listened to our past pet allergy component episode. And if that's you, definitely check that out.
Gary Falcetano:
For sure.
Luke Lemons:
Really good. But components, allergen components, they are part of the whole allergen. So if we think of the whole allergen, let's say the peanut whole allergen, if that's a stew, the molecular components are the egg... Or not the egg, the carrots, the potatoes, the beef that's inside of it. And a patient may be sensitized to only one of those things in that stew like the carrots. But if you only run a whole allergen test, it's going to say you're allergic to stew. It's not going to say, "Hey, you're allergic to the carrots in the stew." And knowing that is helpful because these different molecular components mean different things when it comes to patient management.
Gary Falcetano:
Absolutely. And we know with food allergy in particular, we're talking about an estimated 32 million people in the U.S. with a suspected food allergy. And we have certainly, with 32 million people, and a limited amount of specialists of allergists, it's really incumbent upon all clinicians to help them get to the correct diagnosis as soon as possible. Because it really is impactful for someone's life, whether it's an incorrect over diagnosis or whether it's an incorrect under diagnosis and not realizing you have the allergy. Both are majorly impactful.
Luke Lemons:
And so Gary, can you speak a little bit about the naming convention of these different components? Because we are... In this episode, just to let you know, we're going to be saying a lot of words that sound well, unless you know your Latin, a lot of words that sound made up. But there's a naming convention to these components.
Gary Falcetano:
Yeah. I think in medicine we're used to dealing with the Latin and the Greek roots of a lot of our medical terms and the allergen components, they're really no different. So with these individual components, basically they're named for the Latin name for whatever we're talking about. So for instance, with peanut, Arachis hypogaea, that's the genus and the species of the peanut. The way that we refer to components, because we don't want to say Arachis hypogaea for everything we're talking about, we kind of abbreviate it. And the nomenclature is really the first three letters of the genus. So for Arachis, A-R-A, at the first letter of the species. So it's H for hypogea. And then the number is actually... The number of the component is actually the number it was discovered in. I wish it had more relevance than that, but it's just when the researchers discovered it. So Ara h 1 was the first peanut allergen component that was identified by researchers.
Luke Lemons:
And it also cuts down on confusion where if you're saying Arachis, you're not talking about Dune by Frank Herbert. That's a little joke out there for everyone else who is a sci-fi buff.
Gary Falcetano:
Exactly. At least on this podcast, that means one of us.
Luke Lemons:
Well, looking at... Let's zero in on milk and egg, these allergens or these allergies. And looking at them and understanding their components, we can actually tell if a patient may be able to tolerate baked forms of these foods opposed to fresh forms. Gary, can you tell me a little bit about the milk allergen?
Gary Falcetano:
Yeah. So, when we're talking about milk and egg, but now specifically milk, we know that about 75% of patients who are sensitized to cow's milk can tolerate baked milk. But how do we differentiate those? How can we figure that out? And this is where the allergen components come in.
Luke Lemons:
And I mean, just to go back to that 75% of patients are who are sensitized to cow's milk can tolerate baked milk. That means that three out of four patients that you have that may have cow's milk allergy could potentially be eating cake and cookies and things that they may have been avoiding their whole life. And that's big. But yeah, looking at this allergen, let's figure out why that's the case.
So there's three big allergen components involved here. It's casein, beta-lactoglobulin, and alpha-lactalbumin. Gary, I'm going to let you take the reins on this and explain a little more about what's going on with these different proteins.
Gary Falcetano:
And hopefully my tongue won't get as tied as yours.
Luke Lemons:
Yeah, it's so hard.
Gary Falcetano:
I'll give it a try. So with the... We'll call them the betas and the alphas, the lactoglobulin and the alpha-lactalbumins. They're both proteins that are very heat labile so they can be denatured. And when we are talking about a structure of this protein that's conformational in nature, what that means is when it's highly heated, the protein kind of unwinds from that conformational type epitope and it looks differently. So it's unrecognizable to the patient's specific IgE antibodies.
The flip side of that is casein. So casein is a heat stable protein. It's a more linear epitope that really can't be unwound or denatured by highly heating. Casein proteins typically indicate that a patient will be allergic to all forms of that milk, so both fresh milk as well as highly heated baked milk products.
Luke Lemons:
And we see this similar sort of reaction when it comes to egg allergy as well with their proteins. So there is ovomucoid and then ovalbumin, which is a protein much like beta-lactoglobulin and alpha-lactalbumin. I've got it down now.
Gary Falcetano:
Yeah, you do.
Luke Lemons:
It gets denatured when it comes to heat and digestion, but ovomucoid is heat stable.
Gary Falcetano:
Yeah, that's correct. And it's the same type of structure where ovomucoid is more of a linear epitope. But why is this important, Luke. So I mean, yeah, it's fantastic that a child can eat a cookie or a cake, right, that they previously thought they couldn't. But there's some other kind of attributes or benefits to expanding a patient's diet.
First of all, we love to have people on as diverse diets as possible, but by getting the milk or the egg into their diet in a baked form, if they can tolerate it, there has been some research that showed that it can actually hasten tolerance. So we know a majority of these kids will grow out of their milk or egg allergy by adolescence. Adding a baked form of the food in early can actually kind of hasten that tolerance.
Luke Lemons:
And it's just knowing. Knowing is... Again, we say every time, knowledge is power. And testing these patients to be certain, to be certain they can never have a milk product. Or there may be an opportunity for a baked oral food challenge and a referral to an allergist to figure that out. Understanding this is so important, not just for their health, but just their life in general, their emotional wellbeing. Yeah.
Gary Falcetano:
Sure. And it allows us to give the patients the most information about their current condition. So we also know that ovomucoid, right, the stable egg protein and casein, the heat-stable milk protein are also predictive when patients have elevated levels of those of lifelong intolerance or allergy to those products. Now, not always, right? Because every patient can be different, but they're more predictive of sustained allergy.
Luke Lemons:
And all of these allergens that we're going to be talking about today, if you go to the episode's description, you'll find a link to this episode's webpage. And we will put interpretation guides there that speak a little more about what each of these proteins has to do with the clinical management of a patient.
So let's go into peanut, tree nut and seed, Gary. I think we need to first take another step back and look at the different types of families of proteins that are involved within these types of allergies.
Gary Falcetano:
When we talk about peanuts, tree nuts and seeds, it's a little bit different than the milk and egg because we're not talking about just heat here. But we're also talking about the ability of some of these proteins to be denatured by stomach, stomach acids, pepsin, et cetera. So what happens is... Again, we're talking about the stew, the whole extract of, say, a peanut, it contains many of these different protein families. And some are labile proteins that can be denatured and don't typically cause systemic symptoms. But some are very resistant to any changes of heat and digestion, and they're more closely associated with systemic allergy.
Luke Lemons:
And so the proteins that are often denatured, these are CCDs, which stands for cross-reactive carbohydrate determinants, profilins and PR-10 proteins. So, positivity to these specific components, they help characterize the sensitization as being benign and maybe a lower risk.
Gary Falcetano:
And typically the way patients get sensitized to these are actually through pollens. So CCDs, profilins, PR-10 proteins, they're all pretty ubiquitous in nature. They're found in a lot of plant sources. So plants, plant tissues, plant pollens, as well as plant foods. So that accounts for the cross-reactivity between plant pollens and plant foods such as a peanut. And that can drive a positive whole extract, but may or may not be clinically relevant. And we have to kind of take a deeper dive to figure that out.
Luke Lemons:
And then looking at the more higher risk proteins we have the lipid transfer proteins and storage proteins, which are heat and digestion stable.
Gary Falcetano:
And the lipid transfer proteins are really interesting, not necessarily in a good way, but they have a variable risk profile. So in North America, the lipid transfer proteins have tended to not be that closely related with systemic clinical allergy, although we definitely see it in the southern Mediterranean and southern Italy and Spain. They're highly related to severe allergy. And there's plenty of research ongoing, but we're not quite sure why. What we do know is we're seeing more and more lipid transfer protein allergy in the U.S. that we didn't see before.
Luke Lemons:
And so last episode on ImmunoCAST, we talked about cannabis allergy, and in there we mentioned that we would talk about the LTPs involved with that on this episode. So there's this thing called cannabis food allergy syndrome. Can you explain a little more about that, Gary?
Gary Falcetano:
Yeah, so it does come down to the LTPs. And as I mentioned, the lipid transfer proteins are found in certain foods, tree nuts, peanuts, even wheat, and they're also found in cannabis. So if someone is sensitized to LTPs, there's the potential to actually have a food allergy from these LTPs. And you may have become sensitized because of the cannabis. You may have become sensitized because of an allergy to the LTPs and the food, but either way, you can be sensitized and allergic to both because of those LTPs.
Luke Lemons:
And if you want to learn more about a cannabis allergy, I recommend listening to the episode before this one, but this is about peanuts and tree nuts and seeds. So let's go a little more into peanut. We don't want to talk about every single component, the name of it involved in peanut. But I think some ones that are good to highlight are Ara h 2 and Ara h 6, which are both storage protein components. So they are associated with a higher risk of systemic reaction.
Gary Falcetano:
All of the storage proteins are certainly associated with a higher risk. So in peanut there actually 1, 2, 3 and six are the storage proteins. But as you mentioned, Luke, the two and six are the two S-albumins that have the highest correlation with systemic clinical peanut allergy.
Luke Lemons:
And Ara h 2 has actually been identified as the best clinical marker to help predict peanut allergies in children who were being considered for early peanut introduction.
Gary Falcetano:
And we'll do a whole show on that, or at least part of an episode on the importance of early food introduction to prevent allergy. But yeah, there was this study done not too long ago that actually looked at what the best marker is if you're worried about introducing peanut to a very young, basically an infant, right, in the four to seven to 10 month age frame. What's the best marker to rule out peanut allergies so you can get the early introduction in? And that study by Keat and colleagues actually identified Ara h 2 as the best marker for that.
Luke Lemons:
Looking at some of the profilins and CCDs found also in peanut allergen, there is Ara h 8, which is a PR-10 protein, correct?
Gary Falcetano:
Yeah. Also known as a Bet v 1-homolog. It's got a bunch of aliases.
Luke Lemons:
A lot of different names. We told you there'd be a lot of names coming out in this episode.
Gary Falcetano:
But the bottom line is whether we call it Ara h 8, a PR-10 protein, or a Bet v 1-homolog, it all means that it's a protein that is very similar, phylogenetically, to a pollen protein. So the Bet v 1 is actually a birch pollen component that looks just like Ara h 8 in the peanut. Why is that significant? If you're allergic to birch tree pollen, you have a seasonal allergies in the spring because of that, you may also have a positive peanut test. Most people that are allergic to just Ara h 8, and none of the storage proteins do not exhibit clinical symptoms when eating peanut. Very few may have an oral allergy kind of itchy mouth, but once it gets digested, they have no systemic symptoms. But most have no symptoms at all.
So these, Luke, these are perfect patients to refer to an allergist when we've got this presumptive peanut allergy diagnosis, refer to an allergist so that they can do an oral food challenge, which is kind of the ultimate test. Right? But we can't do them on everyone, especially we don't like to do them on high-risk patients. These are low-risk patients that are perfect candidates for those food challenges.
Luke Lemons:
This is just what's so great about all testing with allergen components is this knowledge. A patient may be sensitized to birch tree pollen and now is showing elevated levels to a peanut allergen test. If you didn't test with allergen components, you may never know that. And there's actually an incredible story. There was this outstanding high school football player who was applying to college. His name is Landon, and he actually has a sensitization to Ara h 8.
Gary Falcetano:
He does, and a few other of the less risky proteins. But the Landon story... I got to know Landon and his mom. Landon's story is an amazing story, and it talks about just how life-changing, getting the right diagnosis is. So if you wouldn't mind, Luke, can I take a minute and tell Landon's story?
Luke Lemons:
Oh, yeah, yeah. It's a great story. I love hearing it.
Gary Falcetano:
All right. So Landon, as Luke said, was an outstanding high school football player. He was preparing, he was applying to multiple colleges, D1 schools, all around the country, including some of the military service academies. And he started getting back all these acceptances. He got an acceptance from a military service academy as well as a bunch of other schools, and was super excited because he really wanted a career in the military. He really wanted to play for the U.S.. And after he got his acceptance, his mom had a quick conversation with the recruiter and she mentioned... She goes, "I'm just concerned. He has a peanut allergy. I want to make sure we can keep him safe while he's away at school." And the recruiter kind of stopped dead in his tracks and said, "I have to call you back." And when he called them back, they said, "I'm sorry. We have to rescind our offer. This is an exclusion. A severe peanut allergy is an exclusion for the military, and we can't bring him into a military service academy."
So Landon and his mom did not... These are not people that just roll over and take these things at face value. So they said, "We want to get to the bottom of things." And if you remember Luke, I was telling you Landon had originally been diagnosed because his dad was anaphylactic to peanuts, had multiple anaphylaxis episodes, and they tested all... His two other brothers, they tested all three of them when they were around the age of two. And they all tested positive for whole extract peanut at pretty high levels. So they just made the presumptive diagnosis at that point, and they avoided peanuts. It Landon's whole life from age two to 18.
Luke Lemons:
Wow. And you said it was whole allergen testing that they used to diagnose?
Gary Falcetano:
Yeah, that's all they had. Peanut component testing was not available when he was two years old.
Luke Lemons:
And so what happens next as they're trying to get to the bottom of this?
Gary Falcetano:
So they found an allergist... Actually, they did a lot of Dr. Google online research, right? And they found out that there's some new testing available, that he may not have it true peanut allergy. He may have outgrown and he may not have had it to begin with, but regardless, they knew that there was more testing now that could be done to try to get to the bottom of his diagnosis.
So they found an allergist. They had the allergen component peanut testing done. He actually came back with very high levels to those less risky proteins, so Ara h 8 and profilins especially were very high. This gave confidence to the allergist that he was seeing that Landon would indeed be able to pass a challenge test. They proceeded with a food allergy oral food challenge. He passed the test with flying colors. He now eats peanut every day and P.S. he's also in the military service academy, and he's doing fantastic.
Luke Lemons:
It's a great story because it shows how this type of testing and also knowledge about these types of components can change lives, change lives. Like you said, his whole life, he had been avoiding peanuts and he had epinephrine auto-injectors, and now he can eat peanuts, he can go to the school that he wants to go to. It's just a great story.
Gary Falcetano:
It is. And as one other footnote to this story, I mentioned his other two brothers were both diagnosed with peanut allergy as well. They're working through figuring out whether they have true clinical peanut allergy or not right now. But while they were doing that, the older brother actually had an anaphylaxis to an accidental ingestion of peanut and then was later tested with components. And those components came back as high risk.
So again, two brothers, two totally different stories, but what that really drives home is they got to the right answers. Right? They kind of confirmed one's peanut allergy and they got rid of another's peanut allergy.
Luke Lemons:
I wonder if there's also a story like this when it comes to some of the other proteins that are out there because we can't hear every person's story. It's great, and hopefully a provider who uses allergen components to test with. So when it comes to the proteins that are mentioned in that story, while different from tree nuts, we see the same sort of high risk and low risk when it comes to the different ones that are found in, let's say, cashews, hazelnut, Brazil nut. They're similar to peanut, but they have different names. And Gary, actually, I think you have a favorite component here in the tree nut category.
Gary Falcetano:
You know I do. Just like we talked about our favorite pet allergen components, Ana o 3, which is the two S-albumin component of cashew, a storage protein, has been my favorite food allergen component since I learned about it years ago. So this component is really cool for a couple of reasons. One, it has a super high predictive value of true clinical cashew allergy. So when we see Ana o 3, even at low levels, it's almost always indicative of a true cashew allergy.
But the other cool part of this component that we don't see in a lot of other components is its ability to predict allergy to another food, and that's pistachio. So pistachio and cashews are so phylogenetically comparable. They have very similar amino acid sequences. Ana o 3 actually predicts pistachio allergy just as well as it predicts allergy to cashew, even though it's a cashew component.
Luke Lemons:
And so they're so closely related. Is it possible for somebody to have a pistachio allergy and not have a cashew allergy?
Gary Falcetano:
Well, we never say never in medicine, right?
Luke Lemons:
Yes. Yeah.
Gary Falcetano:
So it's possible, yes. Probably very improbable and probably pretty rare. We almost always see the two allergies go together.
Luke Lemons:
On this episode's webpage, which again, you can find in the link in this description to this episode, you'll be able to see the interpretation guides for all these different types of tree nuts. And also sesame, which is another allergen that has a component.
Gary Falcetano:
Exactly. The Si-1 component in sesame is another two S-albumins, right? So just like Ara h 2 and six, just like the Ana o 3, and cashew, and those are all... All seem to be pretty bad actors, right? The two S-albumins are typically very highly correlated with true clinical allergy.
Luke Lemons:
And this allergen component and testing for it is important now because sesame is a part of the big nine. It used to be just the big eight, and that includes peanut, tree nut, fish, shellfish, milk, egg, wheat, and soy. These were the big eight allergens that had to be on the back of all food labels. Sesame now joins them. So it's the big nine.
Gary Falcetano:
The big nine, exactly.
Luke Lemons:
So we've talked about a lot of different food allergens today and some of their allergen components. And so to recap, testing for sensitization to allergen components is generally a great thing to do to help improve specificity of a diagnosis and provide clarity to the positives that you may see from whole allergen testing and when history is unclear as well, right, Gary?
Gary Falcetano:
Yeah, and typically, we don't test them in a vacuum. So we know that for the most sensitivity, the whole allergens are still very important. It's when those are positive, and we have an unclear history that the allergen components can really help provide increased specificity and a more precise diagnosis.
Luke Lemons:
And on this episode's webpage, we'll also include a link to the lab ordering guide, which has lab codes for whole allergen testing with reflexes to allergen components. Which is really helpful because you don't have to bring the patient back in to get retested if this whole allergen does come back with elevated levels.
Gary Falcetano:
In general, right, they just help us to better predict how a patient's going to be really clinically respond when exposed to a food. And what does that do? Well for both primary care and specialist, it allows us to be more precise in our diagnosis, more precise in our management considerations, as well as for primary care, making more informed, appropriate referrals to specialists.
Luke Lemons:
And it's all about getting rid of the allergy label when you can. And what I mean by that is, in Landon's case, his whole life, he thought that he was sensitized and allergic to peanut. Because of this sort of testing and because knowledge of these components, he is now able to eat peanut. He's now able to go to the college he wants. And even when it comes to kids who may have a milk or egg allergy, if you don't know which component within those allergens they're sensitized to, you don't know if maybe they're missing out on having a birthday cake or cookies, which is very important to kids. I would argue that most kids, if you asked, would say, that's very important.
So this testing again, is life-changing, and I don't mean that in a sappy sort of way. It really is life-changing because certainty one way or another is important.
Gary Falcetano:
Absolutely.
Luke Lemons:
Thanks for listening to ImmunoCAST today. Again, all the resources are found on this episode's specific webpage at thermofisher.com/immunocast. So that includes the interpretation guides, the lab ordering guide, as well as a link to Landon's story if you want to learn more about that. So thanks for listening.
Gary Falcetano:
Thanks so much. We'll see you next time.
Announcer:
ImmunoCAST is brought to you by Thermo Fisher Scientific creators of ImmunoCAP specific IGE diagnostics and Phadia Laboratory Systems. For more information on allergies and specific IGE testing, please visit thermofisher.com/immunocast.
Specific IgE testing is an aid to healthcare providers in the diagnosis of allergy and cannot alone diagnose a clinical allergy. Clinical history, alongside specific IGE testing is needed to diagnose a clinical allergy. The content of this podcast is not intended to be and should not be interpreted as or substitute professional medical advice, diagnosis, or treatment. Any medical questions pertaining to one's own health should be discussed with a healthcare provider.
