Associations of HLA-A and HLA-B with vancomycin-induced drug reaction with eosinophilia and systemic symptoms in the Han-Chinese population

Chuang-Wei Wang; Wei-Chen Lin; Wei-Ti Chen; Chun-Bing Chen; Chun-Wei Lu; Hsin-Han Hou; Rosaline Chung-Yee Hui; Jennifer Wu; Chih-Jung Chang; Ya-Ching Chang; Wen-Hung Chung; Taiwan Severe Cutaneous Adverse Reaction Consortium

doi:10.3389/fphar.2022.954596

Associations of HLA-A and HLA-B with vancomycin-induced drug reaction with eosinophilia and systemic symptoms in the Han-Chinese population

Front Pharmacol. 2022 Nov 25:13:954596. doi: 10.3389/fphar.2022.954596. eCollection 2022.

Authors

Chuang-Wei Wang^{1

2

3

4

5}, Wei-Chen Lin^{1

6}, Wei-Ti Chen^{1

4

5}, Chun-Bing Chen^{1

3

4

5

7

8

9}, Chun-Wei Lu^{1

4

5

8

9}, Hsin-Han Hou¹⁰, Rosaline Chung-Yee Hui^{1

5}, Jennifer Wu^{1

5

8}, Chih-Jung Chang^{1

11}, Ya-Ching Chang^{1

5}, Wen-Hung Chung^{1

2

3

4

5

7

8

12

13

14}; Taiwan Severe Cutaneous Adverse Reaction Consortium

Affiliations

¹ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan.
² Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.
³ Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
⁴ Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
⁵ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Medical Education, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
⁸ Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁹ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁰ Graduate Institute of Oral Biology, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹¹ Central Research Laboratory, Department of Dermatology and Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, School of Medicine, Huaqiao University, Xiamen, China.
¹² Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
¹³ Department of Dermatology, Ruijin Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
¹⁴ Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.

Abstract

Vancomycin is a commonly used antibiotic; however, it can cause life-threatening severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). A previous study has reported a strong association between HLA-A*32:01 and vancomycin-induced DRESS in European ethnicity. Herein, we aim to investigate the genetic predisposition of vancomycin-induced DRESS in the Han-Chinese population. In this study, we enrolled a total of 26 patients with vancomycin-induced DRESS, 1,616 general population controls, and 51 subjects tolerant to vancomycin. In vitro granulysin-based lymphocyte activation tests (LAT) were conducted among 6 vancomycin-induced DRESS patients who were concomitantly receiving other medicines. HLA-A and HLA-B genotypes were determined by sequencing-based typing. Our results found that vancomycin-induced DRESS was associated with HLA-A*32:01 [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 1.7-35.8; p-value = 0.035], HLA-B*07:05 (OR = 32.3, 95% CI = 2.8-367.7; p-value = 0.047), HLA-B*40:06 (OR = 4.7, 95% CI = 1.3-16.1; p-value = 0.036) and HLA-B*67:01 (OR = 44.8, 95% CI = 7.2-280.4; p-value = 0.002) when comparing the vancomycin-induced DRESS patients with the general population controls. LAT results showed that granulysin significantly increased in the vancomycin-induced DRESS patients upon vancomycin stimulation (4.7 ± 3.7 fold increased), but not upon other co-medicines. This study identified that, in addition to HLA-A*32:01, HLA-B*07:05, HLA-B*40:06, and HLA-B*67:01 were also genetic markers for vancomycin-induced DRESS in the Han-Chinese population. Associations of ethnic variances in HLA with vancomycin-DRESS were observed.

Keywords: HLA; delayed-type drug hypersensitivity reactions; drug reaction with eosinophilia and systematic symptoms; severe cutaneous adverse drug reactions; vancomycin.