An association study of HLA with levofloxacin-induced severe cutaneous adverse drug reactions in Han Chinese
Menglin Jiang,
Jin Yang,
Linlin Yang,
Lina Wang,
Ting Wang,
Shengna Han,
Ye Cheng,
Zihua Chen,
Yu Su,
Lirong Zhang,
Fanping Yang,
Sheng-an Chen,
Jin Zhang,
Hao Xiong,
Lanting Wang,
Zhen Zhang,
Li Ma,
Xiaoqun Luo,
Qinghe Xing
Affiliations
Menglin Jiang
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China
Jin Yang
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Linlin Yang
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Lina Wang
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Ting Wang
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China
Shengna Han
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Ye Cheng
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China
Zihua Chen
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Yu Su
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China
Lirong Zhang
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Fanping Yang
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Sheng-an Chen
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Jin Zhang
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China
Hao Xiong
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Lanting Wang
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Zhen Zhang
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Li Ma
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
Xiaoqun Luo
Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding author
Qinghe Xing
Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China; Corresponding author
Summary: 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∗13:01 (odds ratio [OR]: 4.50; 95% confidence interval [CI]: 1.15–17.65; p = 0.043), HLA-B∗13:02 (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∗13:01 and HLA-B∗13:02 than with non-risk HLA-B∗46:01. Mass spectrometry revealed that nonapeptides bound to HLA-B∗13:02 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.
