{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:53:45Z","timestamp":1760147625343,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Measure of drug-mediated immune reactions that are dependent on the patient\u2019s genotype determine individual medication protocols. Despite extensive clinical trials prior to the license of a specific drug, certain patient-specific immune reactions cannot be reliably predicted. The need for acknowledgement of the actual proteomic state for selected individuals under drug administration becomes obvious. The well-established association between certain HLA molecules and drugs or their metabolites has been analyzed in recent years, yet the polymorphic nature of HLA makes a broad prediction unfeasible. Dependent on the patient\u2019s genotype, carbamazepine (CBZ) hypersensitivities can cause diverse disease symptoms as maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms or the more severe diseases Stevens-Johnson-Syndrome or toxic epidermal necrolysis. Not only the association between HLA-B*15:02 or HLA-A*31:01 but also between HLA-B*57:01 and CBZ administration could be demonstrated. This study aimed to illuminate the mechanism of HLA-B*57:01-mediated CBZ hypersensitivity by full proteome analysis. The main CBZ metabolite EPX introduced drastic proteomic alterations as the induction of inflammatory processes through the upstream kinase ERBB2 and the upregulation of NF\u03baB and JAK\/STAT pathway implying a pro-apoptotic, pro-necrotic shift in the cellular response. Anti-inflammatory pathways and associated effector proteins were downregulated. This disequilibrium of pro- and anti-inflammatory processes clearly explain fatal immune reactions following CBZ administration.<\/jats:p>","DOI":"10.3390\/cells12050676","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:30:35Z","timestamp":1676946635000},"page":"676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HLA-B*57:01\/Carbamazepine-10,11-Epoxide Association Triggers Upregulation of the NF\u03baB and JAK\/STAT Pathways"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4076-821X","authenticated-orcid":false,"given":"Funmilola Josephine","family":"Haukamp","sequence":"first","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe Maria","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-0940","authenticated-orcid":false,"given":"Andreas","family":"Pich","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"},{"name":"Core Facility Proteomics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-3190","authenticated-orcid":false,"given":"Rainer","family":"Blasczyk","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-560X","authenticated-orcid":false,"given":"Florian","family":"Stieglitz","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5826-1989","authenticated-orcid":false,"given":"Christina","family":"Bade-D\u00f6ding","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Simper, G., Celik, A.A., Kunze-Schumacher, R.B.H., Blasczyk, R., and Bade-D\u00f6ding, C. 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