Researchers Identify Possible Root Of Allergies

Allergies, or hypersensitivities of the immune system are more common now than ever before: according to the Asthma and Allergies Foundation of America, one in five Americans suffers from an allergy. Research from Tel Aviv University, recently published in The Journal of Immunology, looked into finding the root of allergies to develop new treatments.

Allergies range from mild forms, such as hay fever, to more severe sensitivities like nut allergies – that can lead to anaphylactic shock. Current medications like antihistamines treat only the symptoms of an allergic reaction, and only a small subset of the dozens of molecules cells release during an allergic reaction.

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Prof. Ronit Sagi-Eisenberg, a cell biologist at Tel Aviv University’s Sackler Faculty of Medicine, believes allergy treatment is too limited. She is working with her Ph.D. student, Nurit Pereg-Azouz, to identify the triggers of allergic reactions to find a way to stop a reaction before it begins. The team hopes that their work will help identify proteins that can be targeted by medications without impacting other cells.

Getting to the root

The answer may lie with the Rab family, a group of 60 proteins that are known to regulate the distribution of proteins throughout the body. The researchers found that 30 of these proteins determine how cells react to an allergen. Two of them have been identified for further research as instruments of preventative medication.

Allergic reactions can appear as rashes, respiratory difficulties or swelling, but they are all caused by the same mechanism. When exposed to an allergen, the body activates the immune system. Mast cells, located throughout the body, sense that the immune system has been mistakenly activated – against something that is not bacterial or viral –  and release biologically active molecules to create an inflammatory response.

So what causes those cells to react? Prof. Sagi-Eisenberg and her team are working to identify the exact chain of events in an allergic reaction. They looked to the Rab family of proteins as a potential source for answers, screening for the proteins’ involvement in initiating the reaction.

“We genetically manipulated mast cells so that they contained mutated versions of these proteins, which were already active without an allergen,” explained Prof. Sagi-Eisenberg. Relevant proteins caused an allergic reaction. “This new methodology allowed us to screen for the functional impact of each member of this family, determining if they either inhibited or activated the allergic process,” she continued. Further research will be conducted to better understand the function of two proteins flagged as especially involved.

Targeted drugs to prevent allergic reactions

An allergic reaction is the result of a chain of events. Researchers can create drugs targeted to break the chain by identifying crucial links. Steroids are the only available type of drug that effectively prevents mast cells from secreting biologically active agents. But they cause harm to kidneys, bones and the immune system. Patients often suffer more from the treatment than from the allergy itself.

“When the chain of events leading up to an allergic reaction can be understood, drugs can be developed to inhibit the initial reaction,” explained Prof. Sagi-Eisenberg. New medications that target tumor cells, for example, are directed at halting the tumor’s ability to grow by starving it of blood and oxygen. Prof. Sagi-Eisenberg envisions similar medications for allergies: ones that address the source of the reaction instead of the symptoms.