August 10, 1995
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Researchers at Johns Hopkins have identified an immune system protein that is linked to severe allergic reactions. The finding should speed development of tests to predict which people are at high risk for severe allergic reactions, and perhaps lead to better treatment, they say.
The protein, called histamine-releasing factor (HRF), appears to determine how severe an allergic response is and how long it lasts, according to a report on the findings published in the August 4 issue of Science.
"With this research, we may not only learn a great deal more about allergies, but also find more effective ways to treat them," says Susan M. MacDonald, M.D., assistant professor of medicine and the first author of the paper.
HRF is one of a family of immune system molecules called cytokines. Many cytokines, including HRF, trigger allergic reactions by causing white blood cells called basophils to release histamine. Histamine, in turn, causes changes in the person's respiratory system that makes breathing difficult.
The Hopkins team recovered HRF from the fluid used to culture immune system cells called macrophages overnight. They also found HRF in the immune system cells called B cells, T cells and mononuclear cells. In addition, they found HRF in fibroblasts, cells that develop into bony tissue, cartilage and other tissues that form the framework of the body and its organs.
Unlike other cytokines, HRF causes basophils to release histamine only when a special type of antibody called IgE is attached to those cells. In addition, not all types of IgE cooperate with HRF to cause histamine release. So the identification of the structure of HRF will let researchers show which people have IgE antibodies that will trigger severe allergies in the presence of HRF. Such antibodies are called IgE+ antibodies, while those that do not respond to HRF are called IgE-.
In order to study the role of IgE in histamine release, they coated basophils with either IgE+ or IgE-. When the researchers added HRF to the basophils, histamine was released only when IgE+ was present.
Histamine is released immediately after a person is exposed to an allergen--an allergy-causing protein--according to MacDonald. The reaction then stops, but recurs hours later because of the presence of HRF. This is called the late phase reaction, and it is similar to serious chronic allergy and asthma.
"Now that we know the structure of a cytokine--HRF--that depends on IgE, we can develop tests to see if a particular person's IgE is sensitive to HRF," says Lawrence M. Lichtenstein, M.D., Ph.D., professor of medicine, director of the Johns Hopkins Asthma & Allergy Center and an author of the report. "Anything that affects the ability of IgE to cause histamine release is important to understanding and eventually treating those allergies."
The current finding comes 10 years after Hopkins researchers found evidence for such a substance.
The research was supported by grants from the National Institutes of Health.