Episode transcript
Time stamps
01:03: Overview of Tree Nut Allergen Components
03:29: Tolerance Development in Tree Nut Allergies
04:21: Explanation of Different Types of Allergen Components
05:38: CCDs and Profilins: Lower Risk Components
06:29: PR-10 Proteins: Lower Risk but Rare Systemic Reactions
07:43: Lipid Transfer Proteins and Storage Proteins: Higher Risk Components
09:02: Storage Proteins and Systemic Allergy Risk
09:53: Reflex Testing and Laboratory Profiles
10:49: Hazelnut Allergen Components
13:36: Walnut Allergen Components
15:17: Cashew Allergen Components
17:00: Brazil Nut Allergen Components
18:03: Summary and Importance of Component Testing
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 and board-certified PA with over 12 years experience in allergy and immunology.
Luke Lemons:
And I'm Luke Lemons with over six years experience writing for healthcare providers and educating on allergies. You're listening to ImmunoCAST, your source for medically and scientifically-backed allergy insights. On this episode of ImmunoCAST, we're going to be discussing tree nut allergen components. Now we've had episodes in the past based on allergen components, specifically peanut allergen components or milk and egg allergen components. But we really want to talk here about hazelnut, cashew, walnut and Brazil nut allergen components. These aren't all the tree nuts that a patient may be allergic to, but these are the ones that as a provider you have readily available component diagnostics.
Gary Falcetano:
Exactly. And these are also some of the most common tree nut allergies as well.
Luke Lemons:
And on top of that, there is actually really high prevalence of patients who do have tree nut allergies. 11% of the global population I believe it is. And it's odd because oftentimes you assume that peanuts might be one of the bigger food allergens that affect people, but in fact, we only see a 6% prevalence on peanuts.
Gary Falcetano:
Those are maximum prevalences. The prevalence varies depending on the populations from as low as 1% for peanuts and 2% for tree nuts. That's still a lot of patients, but we can see as much as you said, 11% prevalence in tree nuts, which is pretty amazing.
Luke Lemons:
And one out of three individuals who do have tree nut allergy may be allergic to another additional tree nut. So a patient you have that may have a hazelnut allergy may also have a Brazil nut allergy. So, there's a lot of overlap here.
Gary Falcetano:
Especially in children. We see that relationship from one tree nut allergy to another in children be as much as 50%. So someone who is sensitized and allergic to one tree nut in children, 50% will have a second tree nut they're allergic to.
Luke Lemons:
And because of this overlap in this prevalence between the different tree nuts, that's why Gary and I thought it would be great to have an episode around component resolve diagnostics for tree nuts. So looking into the specific molecular components that may cause a patient to react, because these components aren't all the same. An individual who's sensitized to a certain component may be a risk for a less severe kind of reaction. So we're going to go in this episode and list off some of these components, but before we do that, we're going to separate them out and look at the four clinical buckets that they kind of fall into because understanding that will help when we discuss what the names of these components are and where they're found in specific nuts.
Gary Falcetano:
Exactly. And you know what, Luke, before we do that, I think it's important too to talk about how significant tree nut allergy is in regard developing tolerances. We know that with milk and egg allergy, the majority of children will develop tolerance and be able to tolerate the food by adolescence. That's not the case with tree nuts. Only about 10% or even a little less than 10% of children will ever develop tolerance once they have an established tree nut allergy. So very significant, potentially lifelong allergy. And that's why it's so important to really get the diagnosis right. And that's what we're going to talk about today when we talk about these protein families and the allergen components that are part of these families.
Luke Lemons:
Exactly. And we will provide an interpretation guide on this episode's specific page, and you can get to that page by going to the link that's in the description of this episode. But stepping again a little bit back, you had mentioned it, there's four types of families or clinical buckets that these components can fall into. Maybe this is your first episode and you're like, what are allergen components? The best way to think of them, let's think of the whole allergen as a stew and it has carrots, it has potatoes, it has beef in it. Those are the components. So pulling out the beef component of the stew or the carrot component of the stew. Likewise, there's hazelnut whole allergen and there's individual components that are a part of it. So let's lay the groundwork to explain where these individual components fall into when we think about a clinical situation.
Gary Falcetano:
And we talk about these clinical buckets or families. Different components are members of those different families. So just like the carrot is in the vegetable family, beef is in the meat family, that's what we're going to talk about. We're going to talk about these individual clinical buckets that different types of allergens that have similar characteristics where they fit in and belong.
Luke Lemons:
So we'll start by looking at the two clinical buckets that if a component falls into these, if a patient is sensitized to this type of component, they may be a lower risk for systemic reaction.
Gary Falcetano:
Yeah. So these two buckets, the first one includes two different families, CCDs and profilins, and these allergen components or molecules are found everywhere. So they're ubiquitous in nature, they're found in plants, plant foods and pollens. And it's usually a pollen sensitization and allergy that causes the associated food with a similar molecule to test positive. So CCDs are cross-reactive carbohydrate determinants. Profilins are kind of ubiquitous as well when these are positive, they're almost never responsible for symptoms of clinical allergy. In the rare cases that they are responsible for symptoms, they're usually oral allergy syndromes or what we call pollen food allergy symptoms. So symptoms around the oral pharynx.
Luke Lemons:
And we'll talk a little bit about pollen food allergy syndrome later in this episode. But the other clinical bucket, a molecular component can fall into is if it's a PR-10 protein. So they're responsible for positive whole extract results typically to tree pollen allergy, birch tree specifically. Patients who have a sensitization to these types of proteins are also at a lower risk of having systemic reactions. However, these proteins may in very rare cases cause a systemic reaction if the body is overwhelmed with them. For example, because these types of proteins are denatured in the digestive system, when there are too many of them in the digestive system, the body might not be able to dissolve them all or digest them. So then you would see a systemic reaction. Again though this is like rare case scenario.
Gary Falcetano:
Exactly, these are pretty rare, but there have been cases in the literature where people who are exclusively sensitized to these PR-10 proteins really overwhelm their body's ability to denature them and they had symptoms, but pretty rare.
Luke Lemons:
And so what is the clinical impact if a patient is sensitized to a protein that falls into one of these two pockets, PR-10 proteins or CCD and profilin?
Gary Falcetano:
Yeah, that's a great question, Luke. Why does it matter? Why do we want to know if they're only sensitized to these proteins? Because if they are, as you mentioned, both the PR-10 proteins and also the CCDs and the profilins, they are denatured by heat and digestion. So typically they're not responsible for almost... They're usually not any clinical symptoms, but as I mentioned, sometimes they are responsible for some localized oral allergy type symptoms. Why is this clinically important? Because these are perfect patients who if they think there might be allergic to this food and we see that they're low risk based upon their sensitization to only these proteins or components that these are perfect candidate for referral to allergy to do an oral food challenge and to actually clear their allergy.
Luke Lemons:
And so the other two clinical buckets that tree nut allergen components may fall into are lipid transfer proteins and storage proteins.
Gary Falcetano:
Yeah. And both of these indicate a higher risk of a systemic reaction. Luke, tell us a little bit about lipid transfer proteins and what we consider an intermediate risk.
Luke Lemons:
They are heat stable and digestion stable. So unlike PR-10 proteins which get denatured in the digestive process, lipid transfer proteins don't, and so that can put a patient at a higher risk of having a severe reaction because the protein isn't destroyed that they're reacting to. There's also a high degree of cross-reactivity between various lipid transfer proteins. This is why we have things like LTP syndrome.
Gary Falcetano:
So LTP syndrome is an allergy where people develop symptoms to multiple foods, both tree nuts, peanuts, fruits, even cannabis. And that's all related to being sensitized to these LTPs and reacting to multiple LTPs when they're encountered.
Luke Lemons:
Storage proteins are also heat and digestion stable as well, and they're found in large amounts in tree nuts. They are very closely related to systemic allergy and it puts patients at a much higher risk for clinical allergy. If you do, let's say a tree nut allergy component test and they are sensitized to a storage protein type.
Gary Falcetano:
We've taken basically four or five different clinical buckets and we've stratified them into less risky proteins. So CCDs, profilins and PR-10 are on the lower risk of the spectrum. And then the LTPs, the lipid transfer proteins and the storage proteins, they're all up on the higher risk end of the spectrum. So again, knowing what your patient sensitization profile looks like really helps you predict how they're going to express their disease.
Luke Lemons:
Exactly. That's beautifully summed up. I think that it's also important to note that when we dive into the names of these specific types of molecular components, that there are profiles out there that reflex to them after the whole allergen. So you're not going to have to take out your pen and paper, write how and write down a bunch of these names, these scientific names to remember to run on an individual patient.
Gary Falcetano:
Yeah, exactly. So when you order the whole extract testing for tree nuts, hazelnuts, walnuts, cashew, if those are positive, most of the laboratories offer a reflex so that you don't have to submit a second order, you don't have to do another blood draw, but the patient's blood will be then analyzed for any components if the initial result to the whole extract is positive.
Luke Lemons:
For example, CCD and profilin you had mentioned it's ubiquitous in nature, it's found in almost all plants. If a patient comes back positive for any sort of tree nut, it will reflex for CCD and profilin. So those types of molecular components will be associated with every tree nut that we talk about here today.
Gary Falcetano:
We always talk about there's being an exception to every rule. So different laboratories set up their different profiles and their reflexes a little bit differently. So some laboratories may or may not offer the CCDs and profilins, but usually they can be added on if they don't, some actually do. So you just need to know your local lab and how it's being offered.
Luke Lemons:
Why don't we dive into the different types of tree nuts and the components that are a part of their whole allergen starting with hazelnut?
Gary Falcetano:
Yeah, absolutely. So hazelnut is a very common allergy. We all love our Nutella, maybe some of the other liqueurs that have hazelnut in it for some of our adult patients. But again, a very prevalent tree nut allergy. When we look at the components, going back to those clinical buckets, the first component, Cor a 1 is a PR-10 protein. So remember PR-10 proteins are the homologous proteins to the birch tree pollens and the Fagalus tree pollens. So sensitization is often precipitated by a pollen or a tree pollen allergy.
Luke Lemons:
It's worth saying too. Again, if you haven't listened to any of our allergen component episodes before, how components are named are the first three letters of the genus of the allergen, and then the first letter of the species, and then a number which indicates when it was discovered.
Gary Falcetano:
The Latin name, right?
Luke Lemons:
Yes, yes. And I know Gary, you're really good at Latin. So for hazelnut, that's…
Gary Falcetano:
Corylus avellana.
Luke Lemons:
Yes. And so Cor a 1, as you had mentioned, is a PR-10 protein. These other molecular components found within hazelnut are the Cor a 8, Cor a 9, and Cor a 14. These are a little more risky for patients to be sensitized to. Cor a 8 is a lipid transfer protein and elevated levels of that type of protein indicate a risk of a systemic reaction. And then Cor a 1 and Cor a 1 14 are storage proteins.
Gary Falcetano:
And they indicate a significant risk of systemic reactions. Remember, the lipid transfers may have a variable risk. One thing we didn't mention when we talked about the lipid transfers, I think bears mentioning, is that the lipid transfer proteins are responsible for a large number of clinical allergy patients in the Southern Mediterranean. So Southern Italy, Southern Spain. But we're starting to see more and more lipid transfer protein allergy outside of those areas. So Northern Europe, North America, we're starting to see more of this. So again, it's just something to be aware of has a variable risk. But the storage protein, so Cor a 9 and 14, those are almost always associated with true clinical allergy.
Luke Lemons:
So if you do decide to test a patient for hazelnut and you get these results back for allergen components, knowing the patient is only reacting or may only be reacting to Cor a 1 is valuable information because there may be some cross reactivity with a birch tree allergen. That may mean that a patient could tolerate hazelnut. If we didn't have the stratification and understanding of which components in an allergen a patient is reacting to, you might be quick to say just avoid hazelnut completely when the patient may not have to do that. That's the clinical value, right?
Gary Falcetano:
I have a fun fact for you, Luke, that I'm going to surprise you with.
Luke Lemons:
Oh, gosh. Okay. What's the fun fact today?
Gary Falcetano:
Walnuts are the oldest tree food known to man dating back to 7,000 BC.
Luke Lemons:
Wow.
Gary Falcetano:
Right. And the Jug r, right? Is the Latin name for walnut. So Juglandaceae regia, right? It actually stems from the Latin, Juglan's regio which means Jupiter's royal acorn. The Romans actually named the hazelnut Jupiter's royal acorn, and that's where the Latin name comes from.
Luke Lemons:
I'm going to start saying that when I'm eating walnuts, it'll seem like I'm very, very cultured. That's a cool name though. I mean, back then people may be reacting to walnut when they would eat it.
Gary Falcetano:
But probably as long as we'd been eating walnuts, there've been some people that have developed allergy for sure.
Luke Lemons:
Yeah. And so looking at the components here too, there's power for walnut, at least there's power in the negative of knowing that a patient isn't showing elevated levels of these two components, which are Jug r 3, which is an LTP lipid transfer protein, and Jug r 1, which is a storage protein. Again, two types of proteins that put patients at a higher risk of having a systemic reaction.
Gary Falcetano:
Exactly. So I think our listeners are kind of getting the idea now, right? If patients are sensitized to the higher risk proteins, this is where we need to take a step back, potentially diagnose the allergy based upon the symptoms and the positive results. Or if they're not sensitized to the high risk proteins, perfect patients to refer for oral food challenges and get their allergy cleared and obviously get them having the most diverse diet possible.
Luke Lemons:
The other treatment we want to focus in on is cashew, and I don't want to speak to this because I know that the component involved within it is one of Gary's favorite components. If you had listened to our last food allergen component episode, I recommend doing that and then you can find out what my favorite component is. But Gary, I'll let you talk here about Ana o 3.
Gary Falcetano:
It is my favorite component, Luke, for a couple of reasons. It really is a very versatile component for a single component. So it's a storage protein. It is this 2S albumin and the 2S albumins in that class of allergens, they seem to have the highest association with true clinical allergy and that's the case with Ana o 3. So I mentioned it's versatile. Sensitization to Ana o 3 can not only diagnose cashew allergy, but also pistachio allergy because the pistachios and cashews are so closely phylogenetically related that Ana o 3 is very predictive of allergy to both. The other thing that I think is just super interesting and useful about Ana o 3 is sensitization at even very low levels. So in one study, a level of 0.16, so barely detectable was associated with a 95% positive predictive value of cashew allergy. So just a great all around component.
Luke Lemons:
I like how you get two for one out of it in a way a patient is results come back and they have elevated levels of Ana o 3, and you can say, "Hey, you may want to avoid cashews and also pistachios." Really interesting.
Gary Falcetano:
Big bang for your buck.
Luke Lemons:
Yeah. Yeah. Two for one. Brazil nut. So this is the last tree nut that we're going to be discussing today. It's component is Ber e 1.
Gary Falcetano:
Yeah. So Ber e 1, once again, a storage protein associated with a higher likelihood of true clinical allergy. And those of you that have listened to some of the previous episodes may remember our Allergy After Dark episode on intimate relations and food allergy, Ber e 1 most likely, but certainly Brazil nut was the cause of a semen allergy in one of those cases we discussed.
Luke Lemons:
And I definitely recommend listening to that episode because it is just really fascinating how this Brazil nut allergen may have been transmitted via human seminal fluid. It's really, really interesting. So definitely check that out. I think ultimately though, it's worth saying again, this isn't all the tree nuts out there that a patient may be allergic to. These tree nuts are the ones that you as a provider have readily available diagnostic testing for. And this also includes the allergen components, the ones that we mentioned today for the specific tree nuts aren't all the molecular components that are found within these nuts, but these are the ones where we have clinical testing for.
Gary Falcetano:
Yeah, and they've been evaluated further clinical utility. Before we close Luke, I just want to reiterate too, the components don't replace the whole extract testing. Whole extract testing is very sensitive, so it helps to pretty conclusively rule out suspected allergies. But when whole extract testing is positive, the clinical picture is a little bit unclear. That's where allergen components can really help us better make the diagnosis and be more specific in the diagnosis.
Luke Lemons:
Yeah, going back to our analogy of the stew, you find out your patient is allergic to beef stew, but it may actually only be the carrots that are in the beef stew. So having this sort of testing is really important to stratify how do you manage a patient. And we will again, have an interpretation guide for these tree nuts on this episode's specific webpage. So if you go to the link in the description of this episode, it should take you there and you can download that and reference some of the things that we discussed today. Also, on that page, you'll find a link to a lab ordering guide, which has test codes for all sorts of different allergen profiles, for labs that are local to you based on your zip code that you may already be using national and local labs. Again, thank you for listening to ImmunoCAST and don't forget to subscribe and share with your fellow clinicians.
Gary Falcetano:
We'll see you next time.
Luke Lemons:
Goodbye.
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.
