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

doi:10.1016/j.isci.2023.107391

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

iScience. 2023 Jul 13;26(8):107391. doi: 10.1016/j.isci.2023.107391. eCollection 2023 Aug 18.

Authors

Menglin Jiang¹, Jin Yang^{2

3}, Linlin Yang⁴, Lina Wang⁴, Ting Wang¹, Shengna Han⁴, Ye Cheng¹, Zihua Chen^{2

3}, Yu Su¹, Lirong Zhang⁴, Fanping Yang^{2

3}, Sheng-An Chen^{2

3}, Jin Zhang¹, Hao Xiong^{2

3}, Lanting Wang^{2

3}, Zhen Zhang^{2

3}, Li Ma^{2

3}, Xiaoqun Luo^{2

3}, Qinghe Xing¹

Affiliations

¹ Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai 200032, China.
² Department of Allergy and Immunology, Huashan Hospital, Fudan University, Shanghai 200040, China.
³ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
⁴ Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

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∗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.

Keywords: Dermatology; Genetics; Health sciences; Immunology.

Associated data

figshare/10.6084/m9.figshare.23311421