A new study has found that the lymphocyte toxicity assay (LTA) may be a useful diagnosis and management tool for drug hypersensitivity reactions (DHRs) in patients with cystic fibrosis (CF).

The study, published in Molecular Diagnosis & Therapy, also found evidence that toxic reactive metabolite accumulation might be part of the event cascade leading to DHRs in patients with CF.

“CF patients are at a higher risk for DHRs compared to the general population, which has been attributed to the recurrent need for antibiotics and the inflammation associated with CF disease,” the authors wrote. “In the current study, we investigated the utility of the LTA test for diagnosis of DHRs in a cohort of CF patients.”

The research team assessed 20 patients with CF who had suspected DHRs to various medications, including penicillins, sulfamethoxazole, meropenem, cephalosporins, rifampicin, vancomycin, and tobramycin, as well as 20 healthy control volunteers. Blood samples were obtained from all included individuals, and the LTA was conducted on peripheral blood monocytes.

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On incubation with the culprit drug, the cells from patients with CF with DHRs had significantly greater cell death than the cells from healthy volunteers. The LTA test was positive in over 80% of cases with a medical history and symptoms consistent with DHRs.   

The authors also observed higher levels of oxidative stress and inflammation in the patients with DHRs, which they suspect could be due to the generation and accumulation of cytotoxic reactive metabolites in patients with CF.

The diagnosis and management of DHRs is challenging, and patients with CF are known to be at greater risk of developing them. Therefore, these promising findings suggest the utility of LTA testing to diagnose DHRs, offering clinicians a tool for early prediction and identification of the problematic drug. However, the small number of patients and the lack of a control group of drug-tolerant patients with CF limits the ability to draw firm conclusions.

Reference

Abuzgaia AM, Elzagallaai AA, Mullowney T et al. Drug hypersensitivity reactions in patients with cystic fibrosis: potential value of the lymphocyte toxicity assay to assess risk. Mol Diagn Ther. Published online March 20, 2023. doi.10.1007/s40291-023-00644-3