UMich researchers use nanoparticles to treat tick-borne red meat allergy

A new strategy of using nanoparticles to prevent a tick-borne red meat allergy has shown promise, according to a study by researchers at the University of Michigan and the University of Virginia. The paper, which was published in Frontiers in Allergy in early August, shows that intravenous injections of nanoparticles into mice can stop them from having allergic reactions to red meat, which could help develop a treatment for humans with alpha-gal syndrome. This syndrome, induced by lone star tick bites, causes a person to become allergic to alpha-gal, which is a carbohydrate found in most mammals. 

A person with AGS could have severe allergic reactions to mammalian meat and products. It can take anywhere from three to six hours to see symptoms of an allergic reaction appear for those with AGS. Though there are treatments available to mitigate the symptoms of AGS, there is no cure.

Jessica O’Konek, co-author and William Chandler Swink research professor, explained how in an allergic reaction, the human body attacks different proteins or sugars, even though they pose no threat. 

“​​The reason that you have an allergic reaction, or even an autoimmune reaction, is that your immune system is targeting things that it should ignore, (that) it should be tolerant to,” O’Konek said. “These (nano)particles are a way that can induce this tolerance that someone has either not gained or that they’ve lost, that’s causing the disease.”

Lonnie Shea, co-author and Steven A. Goldstein collegiate professor of biomedical engineering, described how researchers tested the effect of nanoparticles in mice that were sensitized to alpha-gal through ingestion of beef extract. They found that the nanoparticles significantly reduced their response to alpha-gal. This was measured through multiple immune system factors, including reduced activation of basophils, a type of white blood cell, and decreased release of histamines, a chemical used as part of the allergy response.

“Essentially, the particles really attenuated any sort of response to the alpha-gal,” Shea said. “We were able to really attenuate the response quite substantially.”’

Rackham and Medical student Michael Saunders explained that the nanoparticles, which contain allergens, are taken up by immune cells. Because they lack other molecules that red meat would contain, they prevent a T-cell response.

“The particles themselves are taken up by antigen-presenting cells in your body,” Saunders said. “The T-cells recognize that antigen, and then they become reactive, but they need the right molecular context to become active. … The antigen is presented on the surface of the cell without the other co-stimulatory molecules that prompt T-cell activation. So because of that, you actually promote T-cell deactivation, and then it also promotes regulatory T-cell induction, and regulatory T-cells are basically cells that help knock down antigen specific immune responses.”

In the study, the nanoparticles did not have the same effect in all of the mice, and Shea suggested that this was because the alpha-gal allergy is typically varied, which could have caused different reactions in the mice.

“We saw some mice that were really profoundly improved, and other ones that were not quite as improved,” Shea said. “We think it is the heterogeneity within the model. It might be something as simple as mice that are so reactive could use one or two more doses of the particles. It could be that the basis of the disease might be a little bit different in terms of the immune cells, and those are both great questions for us to continue looking into.”

Saunders discussed how someone might contract the syndrome, and he highlighted the many questions that researchers still have surrounding AGS.

“Our understanding right now is that it is caused by tick bites, typically young ticks in their earlier life stages,” Saunders said. “You probably have to get multiple bites, maybe over time, maybe not, maybe all at once, and then over time you develop the allergies.”

O’Konek emphasized that an allergy to the alpha-gal carbohydrate is different from other allergies which are often linked to specific, known proteins. 

“They become allergic to this one specific sugar, that’s the alpha-gal linkage, but it’s very different from a normal food allergy, which is to protein,” O’Konek said. “With a peanut allergy, we know exactly which proteins people are usually allergic to, same with egg, milk, all those things. But with alpha-gal, it’s this sugar linked to the protein which humans don’t have but almost all other mammals do.”

These nanoparticles have also been used in studies on other allergies, including peanut allergies. O’Konek noted that next steps in this research introduces drug companies, like COUR Pharmaceuticals, which has begun clinical testing nanoparticle treatment for peanut allergies.

Saunders said he could see this research being applicable beyond the treatment of AGS, including to assist with xenotransplants, or organ transplants using living cells or tissue, from animals that have alpha-gal carbohydrates to humans. 

“It is a big issue and a barrier for xenotransplants,” Saunders said. “There are a lot of things that the human body rejects when you get a xenotransplant, but one of the big ones is alpha-gal in that sugar. So it is possible that (this research) could have applications in the transplant space to try to promote immune tolerance in some of those xenogenic organs.”

This is one of the first studies exploring AGS treatment, and according to Shea, many of those living with AGS seem to react positively to the research.

“Since the article has come out, I have been contacted by a number of people who have seen the results and are struggling with the disease and volunteering for clinical studies,” Shea said. “There’s definitely a very affected population out there that’s really looking for solutions. Part of their frustration is there hasn’t been anything, and so I think this is among the first options that is out there that really treats the fundamental source of the disease, rather than just trying to address symptoms.”


Daily Staff Reporter Grace Schuur can be reached at gschuur@umich.edu.

The post UMich researchers use nanoparticles to treat tick-borne red meat allergy appeared first on The Michigan Daily.


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