HLA-A*32:01 Carrier Screening Feasibility Before Lamotrigine, With Matthew Krantz, MD

New data linked HLA-A*32:01 carriage to lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS).1,2

In an interview conducted at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Philadelphia, Matthew Krantz, MD, from Vanderbilt University Medical Center, addressed how these data should guide management decisions and whether pre-prescription screening is feasible. He said a team led by Elizabeth Phillips, MD, from Vanderbilt, had developed a rapid single allele assay for 32:01 that uses allele-specific primers.

“You don’t get full HLA typing, but you get a binary result of whether an individual is a carrier for a 3201 or not,” Krantz said. “You also don't get information if an individual has 2 copies of a 3201; you would only get…that binary result. It's not a clinically available test, but in research settings where it's been optimized, these tests can be done with a several-hour turnaround. We do think that if these tests were to have evidence of meeting that threshold of a low number needed to test to prevent 1 case, that this is something that could be translated into the clinic.”

In the recently published multi-institutional cohort, HLA-A*32:01 was present in 40% of lamotrigine-induced DRESS cases compared with 5.5% of matched lamotrigine-tolerant controls, corresponding to an odds ratio of 12.1 (95% CI, 4.9–29.8; Bonferroni-corrected P < .001). Although this represents a substantial genetic association, DRESS remains rare. Among individuals exposed to high-risk medications for the requisite 2- to 8-week latency period, approximately 1 in 1000 may develop DRESS. At the population level, incidence is estimated at 1 to 3 per 100,000.

Given this low absolute risk, routine pre-prescription high-resolution HLA typing is not currently standard practice. Krantz noted that most patients will not have existing HLA class I data available to guide lamotrigine prescribing. An exception may include patients undergoing bone marrow or solid organ transplantation, where comprehensive HLA typing is already performed.

In situations where HLA-A*32:01 carriage is known, and lamotrigine is strongly indicated, Krantz suggested a risk-mitigation strategy rather than automatic exclusion. Lamotrigine is associated with a spectrum of cutaneous reactions, ranging from mild maculopapular eruptions to severe hypersensitivity. Standard prescribing protocols already emphasize low starting doses with gradual titration to reduce rash risk. In carriers, clinicians could consider even more cautious dose escalation, closer clinical follow-up, and vigilant monitoring for early systemic symptoms such as a rash.

The original cohort included 30 prospectively identified lamotrigine-induced DRESS cases (87% female; 93% self-identified White; median age 33 years [interquartile range, 25–56]) and 300 matched tolerant controls. Krantz acknowledged that the predominantly White, European ancestry composition limits the ability to detect ancestry-specific risk alleles.

“This really requires collaborative networks of academic medical centers identifying and precision phenotyping these individuals, obtaining… genetic data for sequencing, especially for HLA, to be able to generalize these results,” Krantz said. “We're really the first multi-institutional group to kind of show this. The next step would be for replication at other sites.”

Relevant disclosures for Krantz include Silk Road Medical, Inc., Boston Scientific Corporation, and Tactile Systems Technology Inc.

References

1. Krantz M, Gangula R, Yu A, et al. HLA-A*32:01 carriage is associated with lamotrigine-induced drug reaction with eosinophilia and systemic symptoms in a US cohort. Journal of Allergy and Clinical Immunology. 2026;157(2):AB428. doi:https://doi.org/10.1016/j.jaci.2025.12.953

2. Krantz M. HLA-A*32:01 Linked to Lamotrigine DRESS Risk, With Matthew Krantz, MD. HCPLive. Published on February 28, 2026. Accessed on February 28, 2026. https://www.hcplive.com/view/hla-a-32-01-linked-lamotrigine-dress-risk-matthew-krantz-md