Development of label-free electrochemical impedance spectroscopy for the detection of HLA-B*15:02 and HLA-B*15:21 for the prevention of carbamazepine-induced Stevens-Johnson syndrome

Sirinart Chomean; Nontaya Nakkam; Wichittra Tassaneeyakul; Jirapat Attapong; Chollanot Kaset

doi:10.1016/j.ab.2022.114931

Development of label-free electrochemical impedance spectroscopy for the detection of HLA-B15:02 and HLA-B15:21 for the prevention of carbamazepine-induced Stevens-Johnson syndrome

Anal Biochem. 2022 Dec 1:658:114931. doi: 10.1016/j.ab.2022.114931. Epub 2022 Oct 1.

Authors

Sirinart Chomean¹, Nontaya Nakkam², Wichittra Tassaneeyakul², Jirapat Attapong¹, Chollanot Kaset³

Affiliations

¹ Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand; Thammasat University Research Unit in Medical Technology and Precision Medicine Innovation, Thailand.
² Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
³ Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand; Thammasat University Research Unit in Medical Technology and Precision Medicine Innovation, Thailand. Electronic address: chollanotk@gmail.com.

PMID: 36191668
DOI: 10.1016/j.ab.2022.114931

Abstract

Background: Carbamazepine (CBZ) is an FDA-approved anticonvulsant that is widely used to treat epilepsy, bipolar disorder, trigeminal neuralgia and chronic pain. Several studies have reported a strong association between HLA-B*15:02 and carbamazepine-induced Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). However, the HLA-B75 serotype (HLA-B*15:02, HLA-B*15:08, HLA-B*15:11 and HLA-B*15:21) has been found in patients with carbamazepine-induced SJS/TEN.

Methods: This study aimed to develop label-free electrochemical impedance spectroscopy (EIS) for the detection of HLA-B*15:02 and HLA-B*15:21 after PCR-SSP amplification. A total of 208 DNA samples were tested. The impedance was measured and compared to standard gel electrophoresis.

Results: The developed label-free EIS identified HLA-B*15:02 and HLA-B*15:21 alleles with 100% sensitivity (95% CI: 86.773%-100.000%) and 95.05% specificity (95% CI: 90.821%-97.714%), comparable to commercial DMSc 15:02 detection kits.

Conclusions: We successfully developed a novel PCR-SSP associated with signal impedance changes to detect the HLA-B*15:02 allele and HLA-B*15:21 without downstream amplicon size analysis that is suitable for screening individuals before indication of CBZ therapy.

Keywords: EIS; HLA-B*15:02; PCR-SSP; SJS; TEN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticonvulsants / therapeutic use
Benzodiazepines
Carbamazepine* / adverse effects
Carbamazepine* / pharmacology
Dielectric Spectroscopy* / methods
Genetic Predisposition to Disease
HLA-B Antigens / chemistry
HLA-B Antigens / genetics
HLA-B15 Antigen / chemistry
HLA-B15 Antigen / genetics
Humans
Stevens-Johnson Syndrome* / diagnosis
Stevens-Johnson Syndrome* / etiology
Stevens-Johnson Syndrome* / genetics

Substances

Anticonvulsants
Benzodiazepines
Carbamazepine
HLA-B Antigens
HLA-B15 Antigen