Puzzling Together Allergic Reactions

Proteins involved in allergic reactions may provide path to better medications

(RxWiki News) For all the modern marvels of medical science, humans still must contend with allergies, which interrupt work, play and everyday living.

In fact, one in five Americans have some kind of allergy, from the mildly annoying to the potentially fatal.

So scientists are working not only to find better treatments but also to find out how allergies form in the first place to prevent them before they start.

A new study has uncovered one clue in this puzzle by investigating how a group of specific proteins interact with cells - and how two of them might be used in developing new medications to treat allergies.

"Talk to a specialist about managing your allergies."

Professor Ronit Sagi-Eisenberg, a cell biologist at the Sackler Faculty of Medicine at Tel Aviv University in Israel, led a study looking at a group of 60 proteins in the "Rab" family.

Rab proteins regulate how proteins are spread throughout the body, and Dr. Sagi-Eisenberg found in her research that 30 of these in particular relate to how cells react to an allergen.

An allergen, such as pollen or peanuts, is the thing that sets off an allergic reaction. When cells encounter an allergen they are sensitive to, they release dozens of molecules that end up causing the sneezing, red and itchy eyes or other symptoms people experience with allergies.

Antihistamines - the most common and effective treatment for allergies - can only target some of these molecules released by cells. Dr. Sagi-Eisenberg hopes that discovering what leads the cells to release them in the first place may help them develop a medication that prevents the onset of the initial reaction.

In her study, Dr. Sagi-Eisenberg determined that two of the 30 proteins related to a cell's allergen response hold potential for use in a preventive medication.

She hopes that further research will help pinpoint how the allergic reaction progresses so that these two proteins can be used to nip it in the bud.

Scientists do understand the basic mechanism of an allergic reaction. Basically, an allergen sets off the immune system, which then tries to fight off an invader.

But the immune system is designed to fight off viruses and bacteria, not allergens, so another part of the body interferes with the immune system's actions.

Mast cells throughout the body determine that the immune system is fighting something non-viral and non-bacterial and chips in, releasing molecules that cause inflammation. That inflammation is the allergic reaction, whether mild or serious, that people experience.

The question is whether scientists can find a way to stop mast cells from causing that inflammatory response.

"We genetically manipulated mast cells so that they contained mutated versions of these proteins, which were already active without an allergen," said Dr. Sagi-Eisenberg. Proteins that were involved in mast cells' responses would cause an allergic reaction. This let Dr. Sagi-Eisenberg test each protein for its impact.

Once she and her PhD student Nurit Pereg-Azouz identified the 30 proteins that were involved in allergic reactions, they pinpointed the two who were most directly responsible for the reactions - the two they will continue to study for possible incorporation into future allergy medications.

Currently, only one type of medication can stop mast cells from sending out their inflammatory molecules: steroids. But steroids have a range of side effects, causing harm to kidneys, bones and even the immune system, so another type of preventative medication aimed at mast cells would be an important development.

The study was published July 23 in The Journal of Immunology. The research was funded by a grant from the Israel Science Foundation and from a grant from the Constantiner Institute. The authors declared no conflicts of interest.

Review Date: 
August 6, 2012