An association study of HLA with levofloxacin-induced severe cutaneous adverse drug reactions in Han Chinese.

ABSTRACT

Levofloxacin-induced severe cutaneous adverse drug reactions (LEV-SCARs) remain unexplored. An association study of human leukocyte antigen (HLA) alleles with LEV-SCARs among 12 patients, 806 healthy subjects, and 100 levofloxacin-tolerant individuals was performed. The carrier frequencies of HLA-B∗1301 (odds ratio [OR] 4.50; 95% confidence interval [CI] 1.15-17.65; p = 0.043), HLA-B∗1302 (OR 6.14; 95% CI 1.73-21.76; p = 0.0072), and serotype B13 (OR 17.73; 95% CI 3.61-86.95; p = 4.85 × 10-5) in patients with LEV-SCARs were significantly higher than those of levofloxacin-tolerant individuals. Molecular docking analysis suggested that levofloxacin formed more stable binding models with HLA-B∗1301 and HLA-B∗1302 than with non-risk HLA-B∗4601. Mass spectrometry revealed that nonapeptides bound to HLA-B∗1302 shifted at several positions after exposure to levofloxacin. Prospective screening for serotype B13 (sensitivity 83%, specificity 78%) and alternative drug treatment for carriers may significantly decrease the incidence of LEV-SCARs.