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

被引：2

作者：

Jiang, Menglin ^{[1
,2
]}

Yang, Jin ^{[3
,4
]}

Yang, Linlin ^{[5
]}

Wang, Lina ^{[5
]}

Wang, Ting ^{[1
,2
]}

Han, Shengna ^{[5
]}

Cheng, Ye ^{[1
,2
]}

Chen, Zihua ^{[3
,4
]}

Su, Yu ^{[1
,2
]}

Zhang, Lirong ^{[5
]}

Yang, Fanping ^{[3
,4
]}

Chen, Sheng-an ^{[3
,4
]}

Zhang, Jin ^{[1
,2
]}

Xiong, Hao ^{[3
,4
]}

Wang, Lanting ^{[3
,4
]}

Zhang, Zhen ^{[3
,4
]}

Ma, Li ^{[3
,4
]}

Luo, Xiaoqun ^{[3
,4
]}

Xing, Qinghe ^{[1
,2
]}

机构：

[1] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China

[2] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

[3] Fudan Univ, Huashan Hosp, Dept Allergy & Immunol, Shanghai 200040, Peoples R China

[4] Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai 200040, Peoples R China

[5] Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, Zhengzhou 450001, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 08期

基金：

中国国家自然科学基金;

关键词：

TOXIC EPIDERMAL NECROLYSIS; STEVENS-JOHNSON SYNDROME; HYPERSENSITIVITY REACTIONS; SYSTEMIC SYMPTOMS; RISK; HLA-B-ASTERISK-1301; EOSINOPHILIA; ALLOPURINOL; PEPTIDES; ALLELE;

D O I：

10.1016/j.isci.2023.107391

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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.

引用

页数：14

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