BACKGROUND: Severe and potentially fatal hypersensitivity reactions to drugs, particularly antiepileptics, are clinically unpredictable. Recent evidence has revealed a strong and specific association between the implicated drug, the type of adverse reaction, and the particular HLA genotype. An urgent need exists for rapid diagnosis of HLA status to guide drug prescription; however, traditional HLA genotyping has a long turnaround time, is expensive, and is available only in specialized centers. We tested the feasibility of the loop-mediated isothermal amplification (LAMP)-based approach to detect a specific HLA genotype. As an example, we used B*1502, an HLA allele strongly associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, and validated the assay's application as a simple, accurate, rapid, and low-cost blood test for use in both clinical and bedside settings. METHODS: We evaluated B*1502 status with the new LAMP method and compared the results with those obtained by sequence-based typing (SBT) (n = 250) and by sequence-specific primer PCR (SSP-PCR) (n = 200) for 450 samples of DNA (n = 50) and blood (n = 400) from a hematology laboratory. RESULTS: LAMP results showed 100% concordance with both SBT and SSP-PCR results, confirming that LAMP detection of a specific HLA genotype (B*1502 in this case) is an accurate method. All results were available within 1 h. CONCLUSIONS: Our study confirmed that the new LAMP method for detecting a specific HLA genotype is simple, inexpensive, accurate, and rapid, and may be of help in overcoming barriers in effective clinical practice.
BACKGROUND: Severe and potentially fatal hypersensitivity reactions to drugs, particularly antiepileptics, are clinically unpredictable. Recent evidence has revealed a strong and specific association between the implicated drug, the type of adverse reaction, and the particular HLA genotype. An urgent need exists for rapid diagnosis of HLA status to guide drug prescription; however, traditional HLA genotyping has a long turnaround time, is expensive, and is available only in specialized centers. We tested the feasibility of the loop-mediated isothermal amplification (LAMP)-based approach to detect a specific HLA genotype. As an example, we used B*1502, an HLA allele strongly associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, and validated the assay's application as a simple, accurate, rapid, and low-cost blood test for use in both clinical and bedside settings. METHODS: We evaluated B*1502 status with the new LAMP method and compared the results with those obtained by sequence-based typing (SBT) (n = 250) and by sequence-specific primer PCR (SSP-PCR) (n = 200) for 450 samples of DNA (n = 50) and blood (n = 400) from a hematology laboratory. RESULTS: LAMP results showed 100% concordance with both SBT and SSP-PCR results, confirming that LAMP detection of a specific HLA genotype (B*1502 in this case) is an accurate method. All results were available within 1 h. CONCLUSIONS: Our study confirmed that the new LAMP method for detecting a specific HLA genotype is simple, inexpensive, accurate, and rapid, and may be of help in overcoming barriers in effective clinical practice.
Authors: Ana Alfirevic; Munir Pirmohamed; Branka Marinovic; Linda Harcourt-Smith; Andrea L Jorgensen; Tess E Cooper Journal: Cochrane Database Syst Rev Date: 2019-07-17