Intolerance to certain foods can be a literal pain. If you're unlucky enough to have a serious — or even life-threatening — allergy, hope might be on its way. Researchers have discovered a new cell type that appears to drive life-threatening food allergies and may help explain why some people get severe allergic reactions while others do not.
The scientists at Cincinnati Children's Hospital Medical Center say their findings in mice should also provide insights into new therapeutic strategies and diagnostics for food allergies and anaphylactic shock triggered by the immune antibody immunoglobulin E (IgE). The team says they have discovered what they call "IL-9-producing mucosal mast cells." These cells produce large amounts of an inflammatory immune protein called interlukin 9 (IL-9). These "amplify" the anaphylactic shock that occurs in response to certain foods. Before this study, the scientists say, the primary cellular source of IL-9 was unknown.
"Our study suggests that although you need to have some level of IgE to trigger a food allergy response, you also have to produce MMC9 cells to get a severe response and anaphylaxis," says Dr. Yui-Hsi Wang, lead investigator and a researcher in the Division of Allergy and Immunology at Cincinnati. "Without these cells you will not get severe food allergies." The study is published today in the journal Immunity.
Triggered by certain foods like peanuts, shell fish and a host of others, IgE-associated food sensitivity provokes an uncontrolled response in the immune systems of some children. Unless they receive immediate medical treatment, this can trigger a molecular chain reaction in the intestines and other organs — leading to diarrhea, hypothermia, respiratory distress and shock. About 40 percent of children have some IgE-associated food sensitivity, but, says Wang, only 8 percent of that 40 percent develop the severe food reactions that can lead to anaphylactic shock.
Wang and his colleagues suspect that some people are genetically wired to have higher or lower susceptibility to severe IgE-related allergic reactions. Still, it remains unknown exactly how genetics contributes to these molecular chain reactions. "Unfortunately the best medical intervention for these allergies remains avoiding the foods that cause them," Wang says. "We don't know why some patients develop such a strong response and why some don't. This is where we as basic scientists are coming in to see if we can use mouse models to learn this, because mice are very much like humans."
Mice, like people with food allergies, also have different degrees of susceptibility. To investigate this, the researchers studied several different strains of genetically bred mice. The mice were given an egg white protein called ovalbumin to trigger allergic reactions and study their biological reactions. The team observed that after allergic sensitization, some mouse strains generated large populations of MMC9 cells while others did not. The mice that did not produce MMC9 cells exhibited only minor allergic responses whereas the mice that produced intestinal MMC9 cells all had severe allergic reactions. The reactions occurred whether or not they had low or high levels of IgE.
To verify that MMC9 cells were causing severe allergic reactions in the mice, the researchers treated the mice with an antibody that removed those cells, thereby decreasing food allergy symptoms. When MMC9 cells were transferred back into the same mice, the animals' food allergy symptoms returned. The team next looked to see if MMC9 cells are relevant to the development of human food allergies by looking for them in small intestinal biopsy samples from patients with those allergies.
By producing significant amounts of IL-9, the MMC9 cells caused mastocytosis and the production of mast cells — which are known for their role in allergy and anaphylaxis. These may migrate out of the intestines to other organs secreting histamines and other molecules that cause anaphylaxis. The scientists found significantly increased amounts of IL-9 in the samples of food allergy patients, suggesting a possible connection. Wang says his team is now trying to find the human equivalent of the MMC9 cells they found in mice. One goal is to identify the offending cell to see if it possible to create a biomarker that might allow the development of a blood test for food allergies that would allow clinicians to determine which patients are at higher risk for severe food allergies and so improve treatments.