Establishment of the method evaluating the risk for idiosyncratic adverse drug reactions.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670074
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Hiroshi 東京大学, 医学部附属病院, 教授 (80206523)
• Co-Investigator(Kenkyū-buntansha): HONMA Masashi 東京大学, 医学部附属病院, 特任准教授 (60401072)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 薬剤反応性 / 免疫学 / 生体分子 / トランスレーショナルリサーチ

Outline of Final Research Achievements

It has been indicated that genetic backgrounds of patients largely affect the risk for idiosyncratic adverse drug reactions. The interaction between HLA-B*57:01 and abacavir was well characterized and it might trigger immune reactions. We examined whether similar "HLA-drug" interactions are observed in the case of seven combinations of HLA-B genotypes and drugs. As a result, only one combination, B*35:05 and nevirapine, showed the strong interaction as observed in B*57:01 and abacavir. It was assumed that nevirapine associates to the antigen presenting pocket of HLA molecule due to the differences in primary sequence of B*35:05 and its negative control. Indeed, the tendency of peptide repertoire presented by B*35:05 changed in the presence of nevirapine. Refolding experiments using denatured HLA protein also supported this interaction.
On the other hand, it would be need to consider different mechanisms of the interaction in other combinations including B*15:02 and carbamazepine.

Free Research Field

医療薬学