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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.954596

DOI=10.3389/fphar.2022.954596

ISSN=1663-9812

ABSTRACT=<p>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 <italic>HLA-A*32:01</italic> 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. <italic>In vitro</italic> granulysin-based lymphocyte activation tests (LAT) were conducted among 6 vancomycin-induced DRESS patients who were concomitantly receiving other medicines. <italic>HLA-A</italic> and <italic>HLA-B</italic> genotypes were determined by sequencing-based typing. Our results found that vancomycin-induced DRESS was associated with <italic>HLA-A*32:01</italic> [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 1.7–35.8; <italic>p</italic>-value = 0.035], <italic>HLA-B*07:05</italic> (OR = 32.3, 95% CI = 2.8–367.7; <italic>p</italic>-value = 0.047), <italic>HLA-B*40:06</italic> (OR = 4.7, 95% CI = 1.3–16.1; <italic>p</italic>-value = 0.036) and <italic>HLA-B*67:01</italic> (OR = 44.8, 95% CI = 7.2–280.4; <italic>p</italic>-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 <italic>HLA-A*32:01</italic>, <italic>HLA-B*07:05</italic>, <italic>HLA-B*40:06</italic>, and <italic>HLA-B*67:01</italic> were also genetic markers for vancomycin-induced DRESS in the Han-Chinese population. Associations of ethnic variances in <italic>HLA</italic> with vancomycin-DRESS were observed.</p>