Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication
Type B adverse drug reactions (ADRs) are unpredictable based on the drug’s pharmacology and represent a key challenge in pharmacovigilance. For human leukocyte antigen (HLA)-mediated type B ADRs, it is assumed that the protein/small-molecule interaction alters the biophysical and mechanistic propert...
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MDPI AG
2022-01-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/1/40 |
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| author | Funmilola Josephine Haukamp Eline Gall Gia-Gia Toni Hò Wiebke Hiemisch Florian Stieglitz Joachim Kuhn Rainer Blasczyk Andreas Pich Christina Bade-Döding |
| author_facet | Funmilola Josephine Haukamp Eline Gall Gia-Gia Toni Hò Wiebke Hiemisch Florian Stieglitz Joachim Kuhn Rainer Blasczyk Andreas Pich Christina Bade-Döding |
| author_sort | Funmilola Josephine Haukamp |
| collection | DOAJ |
| description | Type B adverse drug reactions (ADRs) are unpredictable based on the drug’s pharmacology and represent a key challenge in pharmacovigilance. For human leukocyte antigen (HLA)-mediated type B ADRs, it is assumed that the protein/small-molecule interaction alters the biophysical and mechanistic properties of the antigen presenting cells. Sophisticated methods enabled the molecular appreciation of HLA-mediated ADRs; in several instances, the drug molecule occupies part of the HLA peptide binding groove and modifies the recruited peptide repertoire thereby causing a strong T-cell-mediated immune response that is resolved upon withdrawal of medication. The severe ADR in HLA-B*57:01<sup>+</sup> patients treated with the antiretroviral drug abacavir (ABC) in anti-HIV therapy is an example of HLA-drug-T cell cooperation. However, the long-term damages of the HLA-B*57:01-expressing immune cells following ABC treatment remain unexplained. Utilizing full proteome sequencing following ABC treatment of HLA-B*57:01<sup>+</sup> cells, we demonstrate stringent proteomic alteration of the HLA/drug presenting cells. The proteomic content indisputably reflects the cellular condition; this knowledge directs towards individual pharmacovigilance for the development of personalized and safe medication. |
| first_indexed | 2024-03-10T01:10:24Z |
| format | Article |
| id | doaj.art-87c9da56a4ef4835a48fa13c4234d6cf |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T01:10:24Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-87c9da56a4ef4835a48fa13c4234d6cf2023-11-23T14:19:34ZengMDPI AGJournal of Personalized Medicine2075-44262022-01-011214010.3390/jpm12010040Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir MedicationFunmilola Josephine Haukamp0Eline Gall1Gia-Gia Toni Hò2Wiebke Hiemisch3Florian Stieglitz4Joachim Kuhn5Rainer Blasczyk6Andreas Pich7Christina Bade-Döding8Institute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstr. 11, 44801 Bochum, GermanyInstitute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyType B adverse drug reactions (ADRs) are unpredictable based on the drug’s pharmacology and represent a key challenge in pharmacovigilance. For human leukocyte antigen (HLA)-mediated type B ADRs, it is assumed that the protein/small-molecule interaction alters the biophysical and mechanistic properties of the antigen presenting cells. Sophisticated methods enabled the molecular appreciation of HLA-mediated ADRs; in several instances, the drug molecule occupies part of the HLA peptide binding groove and modifies the recruited peptide repertoire thereby causing a strong T-cell-mediated immune response that is resolved upon withdrawal of medication. The severe ADR in HLA-B*57:01<sup>+</sup> patients treated with the antiretroviral drug abacavir (ABC) in anti-HIV therapy is an example of HLA-drug-T cell cooperation. However, the long-term damages of the HLA-B*57:01-expressing immune cells following ABC treatment remain unexplained. Utilizing full proteome sequencing following ABC treatment of HLA-B*57:01<sup>+</sup> cells, we demonstrate stringent proteomic alteration of the HLA/drug presenting cells. The proteomic content indisputably reflects the cellular condition; this knowledge directs towards individual pharmacovigilance for the development of personalized and safe medication.https://www.mdpi.com/2075-4426/12/1/40adverse drug reactionHLA-B*57:01abacavirproteomehypersensitivity |
| spellingShingle | Funmilola Josephine Haukamp Eline Gall Gia-Gia Toni Hò Wiebke Hiemisch Florian Stieglitz Joachim Kuhn Rainer Blasczyk Andreas Pich Christina Bade-Döding Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication Journal of Personalized Medicine adverse drug reaction HLA-B*57:01 abacavir proteome hypersensitivity |
| title | Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication |
| title_full | Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication |
| title_fullStr | Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication |
| title_full_unstemmed | Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication |
| title_short | Unravelling the Proteomics of HLA-B*57:01<sup>+</sup> Antigen Presenting Cells during Abacavir Medication |
| title_sort | unravelling the proteomics of hla b 57 01 sup sup antigen presenting cells during abacavir medication |
| topic | adverse drug reaction HLA-B*57:01 abacavir proteome hypersensitivity |
| url | https://www.mdpi.com/2075-4426/12/1/40 |
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