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European Biopharmaceutical Review

Hypersensitivity Reactions

Patients frequently react differently to drugs. An effective treatment for one person may have no impact on someone else, or may even cause adverse reactions. The main cause of these varying effects is the diversity of the human genetic make-up. The field of pharmacogenomics studies these differences and attempts to distinguish individuals who may be harmed by certain drugs from those who may benefit from them by using genetic diagnostic tests.

During the last few years scientists have been investigating the association of specific human leukocyte antigene (HLA) with adverse effects of drugs. In the past, studies utilised HLA serotypes or low resolution genotyping; however, these methods failed to discern the highly complex allelic structure of the HLA genes.

Recently, high-throughput and affordable high-resolution HLA typing has been developed, which allows for genotyping HLA alleles to four digits. These new technologies led to the discovery of a high number of HLA variations which are associated with adverse reactions to various drugs, such as antibiotics and antiretroviral drugs (see Table 1). An example of a striking association is the hypersensitivity reaction to the antiretroviral agent abacavir (ABC) and HLA-B*5701, outlined below.

PREDICTING THE DEVELOPMENT OF HYPERSENSITIVITY REACTION TO ABACAVIR

Abacavir is a nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS (see Figure 1). It is the main active pharmaceutical ingredient in most therapeutics for AIDS patients. Abacavir is an effective antiretroviral drug with excellent long-term safety. The major toxicity of ABC is a hypersensitivity reaction (HSR).


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Dr Birgit Jehn joined QIAGEN GmbH in 2007. Her current role involves the global product management of regulated assays, specifically as applied in the field of solid organ and stem cell transplantations. Birgit studied Biology at the Justus-Liebig- University in Giessen. She received her PhD at the University of Berne in Switzerland in the Institute of Clinical and Experimental Tumor Research.
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