Among the swiftest agents of sudden death is the sting of a bee. A shotof penicillin can also lay low its victim in a matter of minutes. In suchcases, the death certificate reads, "systemic anaphylactic shock."It results, essentially, from an antibody "remembered" and generatedby the recipient of a powerful antigen, such as the bee's venom, or theantibiotic's molecular configuration.What happens is that the clash of antibody and antigen rapidlyunleashes a tremendous crew of immune-system mediators, such ashistamine, serotonin, interleukins and other cytokines that perforateblood vessels, choke airways, disrupt cardiac function and bloodpressure, thus bringing life to an untimely end.Immunoglobulin E (IgE) is the least abundant antibody in the immunesystem; it exists in only trace amounts compared to the other Igs, G, A,M and D. Yet, immunologists hold IgE antibodies responsible for thehypersensitivity that triggers deadly anaphylactic shock. Its less drasticeffects include non-lethal allergic reactions, ranging from a runny noseto asthma.Transgenic mice born without the gene for IgE indicate that othermolecules of the immune system may share this responsibility.At Harvard Medical School and Children's Hospital in Boston, a groupled by Philip Leder (who patented the first transgenic mouse)constructed the population of mice lacking the IgE gene. Of 100embryonic stem cells transfected with null alleles for IgE, six micewere born without the ability to make the antibody. From these, theresearchers bred animals with the targeted IgE-minus mutation.Then they immunized seven of these mice, and also six wild-type ones,with ovalbumin, the highly antigenic protein in egg white. After 18 to21 days, both cohorts got intravenous shots of that protein _ in achallenge roughly comparable to a bee-sting.One minute later, the wild-type animals' hearts began to race, and theirlungs to shut down. All six were dead within 20 minutes. Normal micethat had not received an earlier sensitizing dose of ovalbumin sufferedno ill effects at all.But the seven mutant IgE-deficient animals, contrary to receivedimmunological wisdom, "had the same dramatic response" as the wild-type ones, and six died.Leder and his co-authors reported this experiment in the August 4 issueof Nature, out today. Their conclusion: "Taken together, theseobservations suggest that non-IgE immunoglobulin may be capable ofmediating antigen-specific systemic anaphylactic reactions." The groupis now investigating what alternative immune pathways may take overIgE's role in precipitating immediate, fatal hypersensitivity.Immunologist Albert Sheffer, who heads the immunology and allergyclinic at Boston's Brigham and Women's Hospital (where two of theNature paper's co-authors work) told BioWorld Today:"What's important in their finding is the fact that heretofore it wasalways felt that IgE always had to participate in anaphylactic shock.This is evidence, for the first time in an animal, much less in humans,that there may be other mechanisms for anaphylaxis."It is giving us further insight into the mechanisms of a life-threateningdisorder, and by knowing this we'll be better able to prevent it infuture."Sheffer added that "A significant number of people have idiopathicanaphylaxis _ we don't know why. Then we have a group with bee-sting allergy, from which there are about 50 deaths a year. That's theonly number we have.""This I think is a very fundamental observation. One that will haveclinical implications." n
-- David N. Leff Science Editor
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