New testing approach in HLA genotyping helps overcome 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.
Cheng
Suk-Hang
SH
Departments of Anatomical & Cellular Pathology and Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR.
Kwan
Patrick
P
Ng
Ho-Keung
HK
Ng
Margaret H-L
MH
D000483:Alleles; D004247:DNA / Q000032:analysis / Q000235:genetics; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000191:economics / Q000379:methods*; D012680:Sensitivity and Specificity; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis*; D013997:Time Factors
D006680:HLA Antigens; D015235:HLA-B Antigens; D004247:DNA