AgBioResearch

New research on the causes and effects of wheat allergies is underway at MSU with a study aimed at explaining how various proteins trigger reactions and how best to prevent illness and death in extreme allergic cases.

MSU researchers Venu Gangur, D.V.M., and Perry Ng are leading the project, which has seen several breakthroughs in just the first year.

“We want to understand the immunology of wheat,” said Gangur, associate professor in the Department of Food Science and Human Nutrition (FSHN). “This is a totally new concept. Wheat has become a health issue for a significant number of people in America and around the world. Wheat allergy is potentially deadly. So, what we are doing at MSU is developing and validating a method where we can take a wheat product, test it and determine what the chance is that that product will have the potential to kill someone with wheat allergies.”

The project began with funding from the Michigan Wheat Program and Project GREEEN (Generating Research and Extension to meet Economic and Environmental Needs), an initiative spearheaded by MSU AgBioResearch, MSU Extension, plant agriculture commodity groups and the Michigan Department of Agriculture and Rural Development.

The team successfully created a model using mice to measure the level of allergenicity of wheat varieties. Researchers established that, as the exposure to wheat proteins increases, so does the number of immunoglobulin E antibodies in the blood. Then, they verified that the sensitized mice would display an allergic reaction, resembling a life-threatening reaction in humans.

On the basis of these initial findings, Gangur and Ng received a three-year, $470,000 grant from the U.S. Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) to advance to the current phase of the research.

The goal of the current phase is to validate the mouse model to eventually apply it to human health and use it in the future to test allergenicity of various types of wheat, including potential genetically modified genotypes that are not currently available.

The wheat allergy project

The project recently passed the one-year mark. In that year, researchers have:

• Developed a mouse model for testing wheat allergenicity reactions through skin exposure.
• Established an allergic reaction to wheat in mice through skin exposure as opposed to oral ingestion or injection.
• Discovered that wheat contains certain proteins that can potentially trigger anaphylaxis.
• Established that the four genotypes of wheat in existence may have different allergenicity and developed a model for testing these different wheat proteins in mice.

“The belief was that people develop wheat allergies after they eat it, but the paradigm shift we’ve found is if you take a mouse and feed it wheat, they don’t develop allergies,” Gangur said. “In contrast, if you take mice that have never been exposed to wheat and put a little bit of wheat protein on their skin, they develop allergies. If you administer it orally, they develop tolerance — if you put it on the skin, they develop allergies. That’s our biggest finding so far.

“Imagine if the same thing were to happen in children. They are exposed to wheat all the time. If that were to happen the same way in humans, maybe it explains why people are developing a sensitivity to wheat.”

The mouse model for wheat allergy testing was new when MSU started the project. The university had to breed the mice for the study because other mice available for research had already been exposed to wheat.

“Our mouse model can be used to develop novel methods to prevent and treat wheat allergy, such as vaccines and immunotherapies,” said graduate student Haoran Gao, a food science graduate from China who is working on the project.

MSU’s ability to conduct the wheat allergy study is unique, Gangur said.

“MSU is probably among the very few places on the planet with the capability of doing this type of work,” Gangur said. “We have a multidisciplinary team that can work together to solve a major problem like wheat allergy. We have huge resources and a lot of brain power here.”

The project brings together experts in immunology, medicine, food science, food chemistry, genetics and wheat breeding.

“Dr. Eric Olsen is our wheat breeder,” Gangur said. “He has been extremely helpful in developing and growing this ancient wheat (one of the four genotypes in the study). We’re very excited to have this wheat, which is not grown commercially. Not many people are successful in growing it in amounts that we were able to on campus in our greenhouse.”

In addition to the many researchers and professors on campus, multiple students are participating in the study, including Ph.D. graduate students Gao and Rick Jorgensen, who have contributed to the project from the beginning.

“The students put their blood, sweat, heart and mind in everything,” Gangur said. “We are really grateful to those individuals, and we are fortunate to have worked with them on this project."

History of wheat allergy

Wheat is linked to three health issues: celiac disease, non-celiac gluten sensitivity and wheat allergy. Celiac disease is a well-understood autoimmune disease linked to gluten, but the specifics of non-celiac gluten sensitivity and wheat allergy are less clear.

People allergic to wheat, unlike those with the other two conditions, can have potentially life-threatening anaphylactic reactions. Gangur said the focus for the current study is on wheat allergy to potentially save lives.

“Nobody wants celiac disease or non-celiac sensitivity, but it is manageable through diet, and they are not deadly,” he said. “Wheat allergy is not like that. It can kill you, and people with wheat allergy can’t even be exposed to wheat.”

Allergic reactions to wheat can affect the skin, gastrointestinal system, respiratory system and cardiovascular system. Violent, rapid reactions are what has drawn the attention of the USDA.

“Wheat is generally a very healthy food for about 98 percent of people, but we have this 2 percent that are affected, and that 2 percent could be our loved ones or ourselves,” Gangur said.

There are four genotypes of wheat in existence, only two of which (common wheat for bread, cookies, cakes, etc., and durum wheat for pasta) are being cultivated extensively, and the general public and USDA view all four genotypes as the same, Gangur said. The study aims to use the mouse model to establish whether each of the four wheat types, which are different genetically, are also different in allergenicity.

Ultimately, breaking down the allergenicity of each wheat genotype will allow food distributors to know which wheat proteins are more likely to cause allergic reactions and then potentially generate a shift in production methods that use wheat proteins that are less allergenic.

What's next?

Researchers hope to advance the study to examine the effects of skin exposure on human subjects. Gangur and Ng recently applied for a USDA grant to extend the project and incorporate human testing components.

“Ultimately, we want to make sure it’s relevant to the human situation,” said Ng, professor of cereal science for FSHN.

Jorgensen, a nutritional sciences graduate, said the project is helping the students grow as researchers and will help catapult them toward advancing wheat allergy research as well as other projects in their future.

“It is very exciting for me to be on the forefront of this research,” he said. “Seeing how these proteins interact with antibodies is very interesting, but with our research we can take it a step further and see how these proteins interact with live mice. This allows us to have a better understanding on how these proteins may react within the human body.

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