Objectives: Screening for the HLA-B*15:02 allele has been recommended to prevent carbamazepine (CBZ) - induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) in individuals with Asian ancestry. We aimed, therefore, to develop and validate a robust and inexpensive method for detection of the HLA-B*15:02 allele.
Methods: Real-time PCR using TaqMan® probes followed by SYBR® Green was used to detect the HLA-B*15:02 allele prior to treatment with CBZ therapy.
Results: A total of 121 samples were tested. The assay has a sensitivity of 100% (95% CI: 76.84-100.0%), a specificity of 100% (95% CI: 96.61-100%), a positive predictive value of 100% (95% CI: 76.84-100%) and a negative predictive value of 100.0% (95% CI: 96.61-100.0%), respectively. There was 100% agreement between our results and genotyping using Luminex SSO/SBT/SSP. The lowest limit of detection of the TaqMan® probe is 0.05ng/μl and the SYBR® Green is 0.5ng/μl of DNA. The unit cost of using the TaqMan® probe followed by SYBR® Green is only $4.7 USD.
Conclusion: We developed a novel assay for the detection of the HLA-B*15:02 allele, which is robust, inexpensive and suitable for screening individuals of Asian ancestry in the prevention of CBZ-induced SJS/TEN.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.humimm.2016.08.010 | DOI Listing |
BMC Neurol
September 2021
Department of Neurology, First Affiliated Hospital of Xinjiang Medical University, 830000, Urumqi, Xinjiang Province, China.
Background: The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China.
Methods: We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls.
Medicine (Baltimore)
December 2020
Department of Surgery, Ningbo Municipal Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang, PR China.
Background: Several studies demonstrated a connection between human leukocyte antigen (HLA)-B∗1502 and lamotrigine (LTG)-induced cutaneous adverse drug reactions (cADRs). The correlation between the HLA-A∗24:02 and LTG-cADRs remains controversial. To examine the associations between HLA-A∗24:02 and LTG-cADRs, we conducted a systematic review and meta-analysis.
View Article and Find Full Text PDFTransl Res
May 2012
In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, University of Toronto, and North York General Hospital, Toronto, Ontario, Canada.
Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR). We aimed (1) to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically; (2) to correlate LTA results with the clinical syndrome; (3) to correlate LTA results with the human leukocyte antigen (HLA) allele B∗1502 (HLA-B∗1502) positivity in a Han Chinese-Canadian population; and (4) to determine the cytokine network in this population. Patients that developed fever and cutaneous eruptions in the presence or absence of organ involvement within 8 weeks of exposure to carbamazepine (CBZ), phenytoin (PHY), or lamotrigine (LTG) were enrolled.
View Article and Find Full Text PDFJ Allergy Clin Immunol
June 2012
Molecular Medicine Program, Taiwan International Graduate Program, Taipei, Taiwan.
Background: Increasing studies have revealed that HLA alleles are the major genetic determinants of drug hypersensitivity; however, the underlying molecular mechanism remains unclear.
Objective: We adopted the HLA-B∗1502 genetic predisposition to carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) as a model to study the pathologic role of HLA in delayed-type drug hypersensitivity.
Methods: We in vitro expanded CBZ-specific cytotoxic T lymphocytes (CTLs) from patients with CBZ-induced SJS/TEN and analyzed the interaction between HLA-B and CBZ analogs based on CTL response, surface plasmon resonance, peptide-binding assay, site-directed mutagenesis, and computer modeling.
J Allergy Clin Immunol
March 2011
Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.
Drug hypersensitivity research has progressed enormously in recent years, and a greater understanding of mechanisms has contributed to improved drug safety. Progress has been made in genetics, enabling personalized medicine for certain drugs, and in understanding drug interactions with the immune system. In a recent meeting in Rome, the clinical, chemical, pharmacologic, immunologic, and genetic aspects of drug hypersensitivity were discussed, and certain aspects are briefly summarized here.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!