Mice reveal new, severe form of allergy

As miserable as allergies may be, people can at least try to stay away from the allergens that trigger reactions. But, what if a person is allergic to himself?

Researchers studying an induced condition in mice akin to multiple sclerosis have stumbled across just such a situation. When injected twice with a protein fragment that mimics one of their own, these mice had a severe allergic reaction, according to a report by neuroimmunologist Rosetta Pedotti of Stanford University and her colleagues in the March Nature Immunology. Within 20 minutes, nearly three-quarters of the mice went into a severe reaction known as anaphylactic shock and died.

The findings suggest it’s possible to be acutely allergic to oneself, say the researchers.

Standard allergic reactions are triggered by foreign substances, such as pollen, dust, and foods. These reactions are mediated by histamine, which leads to itching, swelling, and congestion. The most severe reactions can be deadly. In automimmune diseases, such as multiple sclerosis, the immune system kills its own cells, chronically destroying tissue.

“It seems that allergy and autoimmunity are different legs in the autoimmune response,” says Pedotti. In their study, she and her colleagues induced a condition in the mice that serves as an animal model for multiple sclerosis in people. In both conditions, the immune system attacks the sheath of myelin protein around nerves, eventually causing loss of muscle control.

In clinical trials, patients with multiple sclerosis have reported dramatic improvements after receiving injections of a myelin protein, which seem to turn off the autoimmune reaction. This technique is used frequently in mouse studies, but when Pedotti and her colleagues gave mice a second dose of myelin later than usual, the mice responded with full-blown allergic attacks and died. The second myelin dose seems to provoke anaphylaxis, the researchers say.

At this second exposure to the protein, “you are having a shift in the proteins that are used to turn the immune system up or down,” explains Howard L. Weiner of Harvard Medical School in Boston. The study shows “that under special circumstances, you can get allergy or anaphylaxis,” says Weiner.

Pedotti’s group suggests this may have something to do with the presence of myelin protein in the animals’ thymus glands. It’s in this gland that immune cells learn to tell foreign material from self. When the animals’ thymus glands were free of myelin at the time of the second injection, allergic reactions didn’t occur. At 3 to 4 weeks, the injections in the Stanford researchers’ study were later than in standard experiments. So, timing could be the key, the researchers suggest.

Allergy researcher Lawrence M. Lichtenstein of Johns Hopkins University in Baltimore urges caution in interpreting the results. “You can kill a man with a dose of [allergy-inducing] histamine that a mouse can easily tolerate,” says Lichtenstein. “It’s hard to imagine a more different system.”

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