Penicillin allergies may be linked to one immune system gene

Penicillin, effective against many bacterial infections, is often a first-line antibiotic. Yet it is also one of the most common causes of drug allergies. Around 10 percent of people say they’ve had an allergic reaction to penicillin, according to the U.S. Centers for Disease Control and Prevention.

Now researchers have found a genetic link to the hypersensitivity, which, while rarely fatal, can cause hives, wheezing, arrythmias and more.  

People who report penicillin allergies can have a genetic variation on an immune system gene that helps the body distinguish between our own cells and harmful bacteria and viruses. That hot spot is on the major histocompatibility complex gene HLA-B, said Kristi Krebs, a pharmacogenomics researcher for the Estonian Genome Center at the University of Tartu. She presented the finding October 26 at the American Society of Human Genetics 2020 virtual meeting. The research was also published online October 1 in the American Journal of Human Genetics.

Several recent studies have connected distinct differences in HLA genes to bad reactions to specific drugs. For example, studies have linked an HLA-B variant to adverse reactions to an HIV/AIDS medication called abacavir, and they’ve linked a different HLA-B variant to allergic reactions to the gout medicine allopurinol. “So it’s understandable that this group of HLA variants can predispose us to higher risk of allergic drug reactions,” says Bernardo Sousa-Pinto, a researcher in drug allergies and evidence synthesis at the University of Porto in Portugal, who was not involved in the study.

For the penicillin study, the team hunted through more than 600,000 electronic health records that included genetic information for people who self-reported penicillin allergies. The researchers used several genetic search tools, which comb through DNA in search of genetic variations that may be linked to a health problem. Their search turned up a specific spot on chromosome 6, on a variant called HLA-B*55:01.

The group then checked its results against 1.12 million people of European ancestry in the research database of the genetic-testing company 23andMe and found the same link. A check of smaller databases including people with East Asian, Middle Eastern and African ancestries found no similar connection, although those sample sizes were too small to be sure, Krebs said

It’s too soon to tell if additional studies will “lead to better understanding of penicillin allergy and also better prediction,” she said.

Penicillin allergies often begin in childhood, but can wane over time, making the drugs safer to use some years later, Sousa-Pinto says. In this study, self-reported allergies were not confirmed with a test, so there’s a chance that some participants were misclassified. This is very common, Sousa-Pinto says. “It would be interesting to replicate this study in … participants with confirmed penicillin allergy.”

The distinction matters, because about 90 percent of patients who claim to be allergic to penicillin can actually safely take the drug (SN: 12/11/16). Yet, Sousa-Pinto says, those people may be given a more-expensive antibiotic that may not work as well. Less-effective antibiotics can make patients more prone to infections with bacteria that are resistant to the drugs. “This … is something that has a real impact on health care and on health services,” he says.