Home >> ALL ISSUES >> 2018 Issues >> Component IgE testing offers food for thought

Component IgE testing offers food for thought

image_pdfCreate PDF
Amy Carpenter Aquino

November 2018—Food component testing offers improved specificity for distinguishing IgE sensitized from truly allergic patients, and the menu for allergen components may soon expand. “The future will include a lot more component testing,” says Andre Valcour, PhD, MBA, DABCC, vice president and laboratory director of the Center for Esoteric Testing at LabCorp.

“IgE tests are extremely sensitive,” says Anthony A. Horner, MD, associate medical director of immunology, Quest Diagnostics, Nichols Institute. However, “they’re not very specific in that you can have a positive allergy test and not have a true clinical allergy to the food of concern.”

Oral food challenge, the gold standard, is not ideal from a patient perspective and can be deadly. “It takes a long time and it puts patients at risk for anaphylaxis,” Dr. Horner said in a presentation on advances in food allergy testing at this year’s AACC annual meeting.

The true prevalence of food allergy based on oral food challenges is about five percent in children and three to four percent in adults, Dr. Horner said. “[IgE] sensitization rates based on positive allergy tests are anywhere from three to 10 times higher than that, depending on which study you look at.”

Often overlooked is that “this testing is an adjunct to clinical history,” Dr. Valcour said in a recent interview. “In the absence of a positive history of reaction to exposure to a given allergen, a positive IgE test is clinically not relevant. I think a lot of people make that mistake.” Too many doctors, he says, are changing a patient’s lifestyle based on testing with no compelling clinical history. “That’s an unfortunate aspect of this and has to be avoided.”

While component testing is “very much becoming standard of care in Europe,” there is a limited menu—generally confined to peanut, tree nut, milk, and egg components—available through reference laboratories in the U.S., says Dr. Valcour, who is also discipline director of allergy, coagulation, and endocrinology at LabCorp. “We’ll be expanding the current menu of allergen components.”

Component testing for sensitization to red meat, in particular, will become more available in the next year or two, he says. “It’s a very interesting allergy. These patients tend to develop their allergic reaction later, several hours after ingestion of red meat, so people don’t always associate the allergic reaction as being allergy.”

Red meat is an uncommon allergen; it is tolerated even by children who are allergic to milk, egg, or chicken, Dr. Horner said in his presentation. Recent research by Thomas Platts-Mills, MD, PhD, of the University of Virginia, and others found a clustering of patients who had a delayed form of anaphylaxis after ingesting beef or pork in areas with high tick populations. Clinical histories revealed that the patients had had a tick bite in the weeks or months before developing the meat allergy.

“The molecular basis for this is a polysaccharide linkage, galactose-α-1,3-galactose [α-gal],” Dr. Horner said. “Most mammals have the enzymatic machinery to create these linked carbohydrate structures on their proteins, but humans and higher order primates do not.” Alpha-gal is expressed on non-human blood group B antigen and is a major transplantation barrier between primates and other mammals.

“Most of us have IgG to this molecular structure in our blood, but when we eat red meat, we do not have any symptoms,” he said. However, when people produce IgE antibody to carbohydrates containing alpha-gal, there is a risk that the ingestion of red meat will cause an allergic reaction. One theory is that ticks—the Lone Star tick in particular—cause red meat allergy by ingesting blood from a cow or other mammal and then biting a human, which results in skin exposure to the alpha-gal allergen. “The route of exposure, skin versus intestines, is thought to be the reason why anti-alpha-gal IgE is produced instead of anti-alpha-gal IgG,” he said.

Dr. Valcour

Commercial assays to detect IgE to alpha-gal are available, and Dr. Valcour believes physicians will begin to use more component testing for alpha-gal in the next year or so. He also predicts an increase in component testing for venoms, such as wasp or bee venom, and for furry animals, such as cats, dogs, and horses. “One of the dog components, Can f 5, is associated with a prekallikrein, a PSA-like protein, that is secreted by male dogs,” he says. “It seems to be correlated with exposure to male dogs as opposed to female dogs. The clinical utility has yet to be defined, but it may be that some patients are allergic to male dogs and not to female dogs, which is a very interesting story.”

“The bottom line is that there are so many components,” Dr. Valcour says. “Clinical stories are not fully developed for all of them, but over time I’m confident they will be.”

Component testing “helps fill the void” in the search for a better allergen test, though there is room for improvement, Dr. Horner said at the AACC meeting. “Component IgE testing is better than whole allergy testing, at least for some of the foods we are concerned with.”

While food component IgE testing is more specific than whole allergen testing, “there are limitations, such as the fact that most foods are a complex array of proteins,” Dr. Horner said. “More than 130 proteins have been identified in a peanut, for example. About 30 will bind to IgE if you put them on an electrophoresis gel and add patient serum.”

“Not all of the component proteins of a given food are contained in these component panels,” he added. This reduces their sensitivity with respect to IgE detection when compared with the whole food allergen. “Nonetheless, most allergenic proteins are represented in these food component panels.”

If there are 130 proteins in a food item, only some are likely to cause clinical allergy, and there are several reasons. “The relevant abundance of each of these proteins is a consideration,” as is the nature of the binding interactions between IgE and some of the proteins. Many foods contain highly cross-reactive proteins. “But IgE affinities to these cross-reactive proteins are often weak. Therefore, IgE reactivity to select food component proteins is strongly associated with having an allergic reaction, while IgE reactivity to others is not,” Dr. Horner said.

Then there are the component’s physical characteristics. Proteins that are resistant to heat and/or enzymatic digestion in the intestines are far more likely to be allergens and cause clinical symptoms than foods that are readily digested.

“There’s good data supporting the use of component testing for at least some of the foods,” Dr. Horner said, adding that the data most strongly support component testing for allergy to peanut, hazelnut, milk, egg, and wheat.

Although a peanut is a legume and more closely related to soy and peas than to tree nuts, it shares features with tree nuts: All contain profilins and storage proteins. Peanuts and hazelnuts contain the pathogen-related protein 10 (PR-10 protein), and peanuts, hazelnuts, and walnuts contain transfer proteins.

“Peanut and tree nut storage proteins are generally the most highly allergenic because they are resistant to heat denaturation and enzymatic digestion,” Dr. Horner said. “The good news is there’s not a lot of cross-reactivity between these storage proteins. Although if someone’s allergic to walnut, they’re likely to be allergic to pecan because these storage proteins do have a fair amount of cross-reactivity in terms of IgE.” The same can be said for cashew and pistachio.

The lipid transfer proteins are expressed by a variety of plant foods as well as tree and wheat pollens, and they’re found in fruits, nuts, and vegetables. “The degree of cross-reactivity in this family of proteins is varied,” he said, “but they are fairly stable to heat in enzymatic digestion, so they have been associated with allergic reactions in some patients.”

PR-10 proteins are more cross-reactive and less likely to be associated with severe allergic reactions. These proteins, particularly in the case of peanut, cross-react with birch pollen, which explains why some people who are allergic to trees will develop oral allergy symptoms when they ingest tree nuts or peanut. They’re rarely associated with systemic reactions.

The profilins “are probably the most promiscuous when it comes to cross-reactivity,” Dr. Horner said, and the least likely to cause severe allergic reactions.

Peanut is the best example of the utility of nut component testing. “Approximately 10 percent of American children have a positive IgE response to peanut if tested with whole anti-allergen, but they don’t necessarily develop symptoms,” he said. For children who do not develop allergic symptoms, the recommendation is to continue eating peanuts because it can help maintain tolerance.

“There are concerns that if the child begins avoiding these foods, the chances of becoming clinically allergic over time actually increase.”

In contrast to these children who are sensitized, he said, about two percent of children have true peanut allergies. “These are patients who have the positive allergy IgE test results for whole allergen, and they develop immediate clinical symptoms after ingestion.” Unlike for sensitized children, the recommendation for these children is to avoid peanut ingestion and to carry EpiPens.

“It’s important to get it right and to be able to distinguish these two patient groups,” Dr. Horner said. Component testing can be helpful but does not have the diagnostic accuracy of an oral food challenge.

CAP TODAY
X