Friday, June 1, 2012

Component Testing (Pt.2) - Why Should We Care?

So, in Part 1 of this labor of love, I talked about EIA vs. component testing for allergies. If you followed the science, you can start to see some situations where component testing might be helpful to figure out what's going on with our kids:

1. To identify cross-reactivity between food and pollen.

There are six peanut allergens that are currently the focus of component testing: Ara h 1, 2, 3, 5, 8 and 9. It's important to note that there are at least 24 identified, potentially allergenic epitopes just for Ara h 1!

The first three are what are known as seed storage proteins. They're important to the plant to ensure the next generation of little plants is grown. As a result, they're extremely durable and usually make it intact through break-down process in the stomach. Ara h 9 is a lipid transfer protein, responsible for moving fats across membranes within the cell. Again, it's a pretty hardy little beast.

In contrast, Ara h 5 and 8 are wimps. They also have homologues across many other plants, especially pollen from those plants, so the chances of cross-reactivity on a traditional allergen panel are high.

The traditional method of testing that uses a natural extract cannot tell these two types of results apart. One recent study showed that 11.8% of kids tested using a traditional RAST test showed up positive for peanut. However, when challenge tests were conducted, only a quarter of the kids actually reacted when they ate peanut. This roughly correlates with the estimated 1-2% rate of peanut allergy in the population.

The uKnow test is currently being marketed to parents whose kids had a positive peanut test but who have  never experienced an actual reaction to peanut. If you are in that category, this test could change your life.

Remember those look-alike proteins, or homologues? In the case of kids who test positive, but who really don't have a peanut allergy, there's a distinctive pattern that shows up:

Remember that Ara h 8 is a wimp. It mostly breaks down in the stomach to the point that the body doesn't react to it. That's why it often causes an itchy mouth but limited other symptoms.

This may be the explanation for the fabled "mild" peanut allergy. These kids will all have itchy mouths. Some of them may even have a few systemic symptoms. But, the thought is that they are not likely to tip over into serious anaphylaxis. (Of course, whether you're ready to turn in your epinephrine injector under those circumstances is between you and your doctor.)

Another great example of where the test is useful is my son's situation. His January RAST for hazelnut was ~3, yet the RAST just taken for the FAHF-2 study in April was a 12. That's a huge increase for a RAST in just four months!

It turns out that hazelnut (Cor a 1) and Birch (evil birch Bet v 1!) are strong homologues.1 The large increase in his number during tree pollen season is a good indicator that we're probably looking at a less serious form of hazelnut allergy. We're hopeful that a component test can take this worry off his plate.

2. Possibly: to provide more information on the timeline to outgrow milk/egg allergy.

Milk and egg allergies are really tough on parents! For 17 years now, we've asked the question of our allergist that I'm sure all of you MA/EA parents ask each time: "when will my kid OUTGROW this allergy?!"

There are some things scientists have found out about these allergies. As with peanut, if kids are allergic to multiple allergenic proteins, it generally makes the allergy more persistent. Additionally, if a child's body can recognize epitopes when they're not folded up in a protein, that also means they're likely to have the allergy longer, maybe lifelong, and potentially have more serious reactions.

A traditional RAST test can crudely test for the different components of milk: whey, casein, α-lactalbumin, β-lactalbumin, but it can't identify specific epitopes and it can't demonstrate whether the allergy is to "folded" proteins (not as bad) or the "unfolded" strand of protein (bad). The component test, though, gets down to just the very small (sometimes just 10 amino acids) unfolded "hot spot" on the protein that's causing the problem.

For milk and egg, there are "hot spots" that have been associated with severe, persistent allergies. For egg, these hot spots are all on a protein called ovomucoid.2  For the persistent milk allergy kids, the epitopes were associated with the casein protein.3

So is this test really able to tell which kids will outgrow their milk and egg allergies? The answer is maybe. Some doctors are already using it to look at patterns in milk/egg and determine whether introducing baked milk will be helpful in speeding up the tolerance process. It's definitely something to ask your allergist about.

NOTE: Right now, ISAC (Immuno Solid Phase Allergen) testing is being done by one experimental laboratory (Phadia), with only 103 components from 47 allergens available.4  Your allergist may not have a relationship with this lab or be ready to roll this out to patients.

3. Future hope: to separate "potent" epitopes from less harmful ones and find the pattern for life-threatening allergies.

This is where we start to get into weighing the cost of the test against the information it provides. If you have a child who has already experienced a reaction to peanut, why might you want to have the test done?

So far, 95% of people who react to peanut in real life and who have had component testing show a sensitivity to Ara h 2. However, there also seems to be a correlation between how many epitopes of peanut you're allergic to and how allergic you are.5  The current theory for why is related to T cells, the first type of immune cell that responds to the allergen. (The Allergist Mom just did an awesome post on all the science behind this if you are interested.)

T cells are specific to the epitopes to which they bond, but the T cells all compete for the same pool of resources (the "antigen presenting cells" Allergist Mom mentions). Like fighting kids, they're fine if they think all the toys in the room are available to them, but when they see other kids who might want the same toys, they get upset and all hell breaks loose. So...the more epitopes a peanut-allergic person is sensitized to, the more likely it is that their reaction will be severe.6 

However, so far there is no "smoking gun" epitope, or pattern of epitopes on any of the allergenic proteins, that signals potentially fatal reactions. Like fingerprints, the patterns from person to person can be very different. Scientists are still busily identifying and characterizing all the epitopes for peanut. Plus, different populations show different patterns of epitope sensitization, and even allergen sensitization (for example, Ara h 9 is more prevalent in Mediterranean populations). In order to answer these questions, they'll need a lot more data from people willing to take the test. However, those people taking the test will probably not benefit right away.

Are you willing to spend the money to get a picture of your kid's epitope "fingerprint", even though the data to understand what it means is not yet available? We're still thinking about this one.

4. Future hope: to help determine potential pitfalls for MFA kids.

When my son was around age 4, we went through a horrible period where we thought he had idiopathic anaphylaxis. Instead, it turned out that he had developed allergies to a wide range of legumes. The probable culprit? Ara h 1, which shares a seed pod protein with many other legumes.

The problem is that not all kids who are positive for Ara h 1 have allergies to other legumes! There's likely some other mechanism involved in sensitizing children to these look-alike proteins. (Remember the faces from the homologue example? Some people are just better at telling faces - and proteins - apart than others.)

This test has great potential to eventually tease out these linked proteins, far better than the crude botanical family relationships many of us use today. It's definitely not ready for prime time. But maybe someday soon, your doctor will be able to look at your child's peanut epitope pattern and make a good guess as to which tree nuts may or may not be a problem.

So...all in all, component testing is promising...but probably not 100% there yet for anything except for identifying those peanut allergies that are most likely cross-reactions to pollen. But what a gift this will be to those parents who are terrified their child is peanut allergic on the basis of testing only! And apparently, that's a good percentage of the kids out there.

PLEASE NOTE: these are MY thoughts on the value of this testing only. You should definitely discuss this with your physician. Additionally, I would love to hear from others interested in the science as to how they see this playing out in future.

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