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

iScience (Aug 2023)

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

Journal volume & issue: Vol. 26, no. 8
p. 107391

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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