Essential 'Allergy Feedback Loop' Discovered By Hopkins

Blood test results from hayfever victims testing an experimental anti-allergy drug have led investigators at the Johns Hopkins Asthma and Allergy Center to discovery of an essential immune system feedback loop that appears to be a basic mechanism driving all allergies.

The biochemical loop, the scientists say, links the amount of immunoglobulin E (IgE) antibody, overabundant in people with allergies, to the number of immune cell IgE receptors, which, upon exposure to allergens, trigger a cascade of biological events that cause wheezing, sneezing, itching and swelling so common this time of year.

When volunteers took an experimental anti-IgE drug, the amount of circulating anti-IgE dropped by as much as 99 percent. But the Hopkins team, led by Donald MacGlashan Jr., M.D., Ph.D., suspected another factor contributed to the drug's anti-allergy effects.

They were right. In 1997 the team found the number of IgE receptors on certain immune cells plummeted alongside the drop in IgE, like two rocks rolling down the same hill. Together, the decreases stanched the allergic cascade, preventing symptoms in patients in clinical trials of the drug.

Continuing this work in the current study, the team discovered that when patients stopped taking the drug, not only did IgE bounce back to pretreatment levels, but immune cells sprouted new receptors, increasing from just a few thousand per cell to pretreatment levels of 200,000 or more over a few months.

The Hopkins team documented this feedback loop in lab tests and, for the first time, in patients, confirming what they had long suspected: that IgE antibodies and IgE receptors wax and wane together, linked somehow in a complex dance.

"To stop allergies, you need to maintain low counts of both IgE antibodies and IgE receptors," says Sarbjit Saini, M.D., lead author on the study, which appears in the May Journal of Immunology. "A slight increase in eit

Contact: Brian Vastag
Johns Hopkins Medical Institutions

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