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• W2891274966 abstract "Among patients treated with the anticonvulsive and psychotropic drug carbamazepine (CBZ), approximately 10% develop severe and life-threatening adverse drug reactions. These immunological conditions are resolved upon withdrawal of the medicament, suggesting that the drug does not manifest in the body in long term. The HLA allele B<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M2><mml:mo>∗</mml:mo></mml:math>15:02 has been described to be a genomic biomarker for CBZ-mediated immune reactions. It is not well understood if the immune reactions are triggered by the original drug or by its metabolite carbamazepine-10,11-epoxide (EPX) and how the interaction between the drug and the distinct HLA molecule occurs. Genetically engineered human B-lymphoblastoid cells expressing soluble HLA-B<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M3><mml:mo>∗</mml:mo></mml:math>15:02 molecules were treated with the drug or its metabolite. Functional pHLA complexes were purified; peptides were eluted and sequenced. Applying mass spectrometric analysis, CBZ and EPX were monitored by analyzing the heavy chain and peptide fractions separately for the presence of the drug. This method enabled the detection of the drug in a biological situation post-pHLA assembly. Both drugs were bound to the HLA-B<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M4><mml:mo>∗</mml:mo></mml:math>15:02 heavy chain; however, solely EPX altered the peptide-binding motif of B<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M5><mml:mo>∗</mml:mo></mml:math>15:02-restricted peptides. This observation could be explained through structural insight; EPX binds to the peptide-binding region and alters the biochemical features of the F pocket and thus the peptide motif. Understanding the nature of immunogenic interactions between CBZ and EPX with the HLA immune complex will guide towards effective and safe medications." @default.
• W2891274966 created "2018-09-27" @default.
• W2891274966 creator A5010671189 @default.
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• W2891274966 date "2018-09-13" @default.
• W2891274966 modified "2023-10-17" @default.
• W2891274966 title "Carbamazepine-Mediated Adverse Drug Reactions: CBZ-10,11-epoxide but Not Carbamazepine Induces the Alteration of Peptides Presented by HLA-B<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:mo>∗</mml:mo></mml:math>15:02" @default.
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• W2891274966 doi "https://doi.org/10.1155/2018/5086503" @default.

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