Researchers identify possible genetic component of penicillin allergy
Research Activities, January 2009, No. 341
A new study of clinical and genetic factors associated with penicillin allergy found that several variants in the gene for interleukin-4 (IL-4), a protein that stimulates the immune system, significantly increased the risk of this allergy beyond the presence of two clinical risk factors. Penicillin allergy is a clinical diagnosis, typically based on self-report by the patient, because accurate skin tests for this allergy are not commercially available. A tenth of hospitalized patients report being allergic to penicillin and allergic events occur in 2 percent of penicillin treatments, but deaths from this allergy are rare (estimated at 1-2 deaths per 100,000 courses of penicillin treatment).
Researchers at the University of Pennsylvania Center for Education and Research on Therapeutics (CERT) and colleagues used data from a case-control study comparing 23 adults with and 39 without a history of clinical penicillin allergy. They identified several clinical and genetic factors that were associated with self-reported penicillin allergy. The significant clinical factors were a history of penicillin allergy among close relatives, a personal history of having other adverse drug reactions, and a history of developing allergies to common environmental allergens (such as allergic rhinitis or bronchial asthma).
The researchers selected candidate genes (IL4, IL4R, and IL10) that code for proteins involved in allergic reactions, and a gene (LACTB) for an enzyme that governs penicillin metabolism. Comparisons between cases and controls suggested that penicillin allergy was significantly associated with the presence of three variants in the IL4 gene, but not IL4R or IL10, and marginally associated with a variant in LACTB.
The researchers note that penicillin sensitivity appears to be influenced by multiple genetic and environmental factors that can make the allergic response vary over time. Future research may determine if the influences of genetic and environmental factors similarly play a role in other immediate allergic reactions such as bee- and wasp-sting allergy.
The study was funded in part by the Agency for Healthcare Research and Quality (HS10399) to the University of Pennsylvania CERT. For more information on the CERTs program, please visit http://www.ahrq.gov/clinic/certsovr.htm.
More details are in "Clinical and genetic risk factors of self-reported penicillin allergy," by Andrea J. Apter, M.D., M.Sc., Heidi Schelleman, Ph.D., Amy Walker, B.S., and others, in the July 2008 Journal of Allergy and Clinical Immunology 122(1), pp. 152-158.