Study sheds new light on penicillin allergy

Scientists have reported the first strong evidence of the role of HLA-B, a crucial histocompatibility complex gene, in penicillin allergy.

Penicillin

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To predict genetic risk factors for penicillin allergy, the international group of scientists harnessed self-reported data as well as the electronic health records of over 600,000 individuals. The researchers have also reported their findings in two separate research cohorts that involved over one million individuals.

Kristi Krebs, Ph.D., from the University of Tartu based in Estonia, presented the study results at the American Society of Human Genetics 2020 Virtual Meeting.

Penicillin is not only a life-saving antibiotic but is also the most common cause of drug allergy, with side effects varying from temporary skin reactions to systemic syndromes that can be life-threatening. But the role of genetic factors affecting the susceptibility to penicillin allergy continues to remain largely vague.

Dr. Krebs and her collaborators gathered information from the electronic health records of over 600,000 individuals of European ancestry from Estonia, the United Kingdom, and the BioVU biobanks of Vanderbilt University Medical Center. They performed a genome-wide association analysis in all three cohorts and the outcomes were further meta-analyzed.

The studies showed a strong signal arising from the human leukocyte antigen (HLA) area on chromosome 6. HLA is essentially the human version of the main histocompatibility complex (MHC)—a gene group that manifests in several species. This gene group plays a role in the ability of the immune system to differentiate the body’s own proteins from proteins created by foreign invaders, like bacteria and viruses.

The researchers precisely mapped the association that allowed them to narrow the signal down to a particular version of the HLA-B gene—an allele known as HLA-B*55:01 with a 2% average frequency in the European population.

Overall, carriers of this allele were found to have 33 percent higher relative odds of penicillin allergy.”

Kristi Krebs, PhD, University of Tartu

As the last step, the team carried out a replication of the association between the penicillin allergy and the HLA-B*55:01 alleles in two separate research cohorts totaling over 1 million people. The researchers again detected a strong link between the HLA-B*55:01 alleles and the self-reported penicillin allergy.

According to Dr. Krebs, more studies are required to establish the accurate immune processes that play a crucial role in penicillin allergy and to gain a more clinically actionable understanding of genetic risk factors underlying the hypersensitivity reactions to the penicillin drug.

Dr. Krebs added, “This discovered association between the HLA-B*55:01 alleles and penicillin allergy would need further in-depth research on the specific types of penicillin-induced hypersensitivity reactions.”

Studying both severe and milder types of hypersensitivity reactions could help reveal the mechanism behind the role of the HLA-B*55:01 allele in this condition and to determine the precise underlying immune processes.”

Kristi Krebs, PhD, University of Tartu

The study demonstrates the power of biobanks associated with electronic health records and shows that by taking advantage of the data from large-scale cohorts, one has the required means to perform studies on penicillin allergy as well as for other serious drug reactions in the days to come.

Source:
Journal reference:

Krebs, K., et al. (2020) Genome-wide Study Identifies Association between HLA-B∗55:01 and Self-Reported Penicillin Allergy. The American Journal of Human Genetics. doi.org/10.1016/j.ajhg.2020.08.008.

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