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

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  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 Hou  10 , 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

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 et al. Front Pharmacol. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Lymphocyte activation test (LAT) for patients with vancomycin-induced DRESS. Granulysin-based lymphocyte activation test (LAT) was performed in 6 patients with vancomycin-DRESS and 5 tolerant controls. A positive result was defined as a 1.4-fold increase in granulysin release compared to the tolerant controls (dotted line).
See this image and copyright information in PMC

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