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Clinical and Translational Allergy

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Open Access

The HLA library for drug screening in preventing severe drug hypersensitivity

  • Chun-yu Wei1
Clinical and Translational Allergy20144(Suppl 3):P51

https://doi.org/10.1186/2045-7022-4-S3-P51

Published: 18 July 2014

Background

The clinical and economic impact of severe drug hypersensitivity is huge for both healthcare and pharmaceutical industry; however, no method for predicting culprit candidate t drugs under clinical development exists currently. As genetic variants in human-leukocyte antigens (HLA) have been linked to inter-individual differences in the risk of drug hypersensitivity, we ascertained whether HLA library can serve as a drug screening tool for their potential to cause severe drug hypersensitivity.

Method

We cloned and generated stable cell lines expressing one common HLA allele, and then purified each HLA protein genetically linked to particular hypersensitivity, immobilized on a protein chip and analyzed the interaction between HLA and drugs by surface plasmon resonance (SPR) analysis.

Results

With HLA library coating on the chip, the direct interaction between specific HLA protein complexes and culprit drugs were detected by SPR analysis. For example, HLA-B*1502 protein interacted with aromatic anti-epileptic drugs, such as carbamazepine (CBZ), CBZ analogs (10,11-eposide CBZ, oxcarbazepine, licabazepine and eslicarbazepine), phenytoin (PHT), and lamotrigine (LTG), but not structure-unrelated compounds, such as gabapentin (GBP), levetiracetam (LEV), and topiramate (TPN); In addition to HLA-B*1502, other HLA-B75 members could also present CBZ, whereas HLA-B62 and HLA-B72 members could not, consistent with pharmacogenetic data. Moreover, HLA-B*5801 binds to allopurinol and oxypurinol, but not febuxostat. Similar, HLA-B*5701 could interact with the nucleoside reverse transcriptase inhibitor, abacavir, but not the non-nucleoside reverse transcriptase inhibitor, nevirapine.

Conclusion

These data suggested the possibility of using HLA library which contains different HLA molecules for its ability to bind drug as a screen tool to screen drugs for their potential to cause severe drug hypersensitivity.

Authors’ Affiliations

(1)
Institute of Biomedical Sciences/Academia Sinica

Copyright

© Wei; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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