English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Carbamazepine-mediated adverse drug reactions: CBZ-10,11-epoxide but not carbamazepine induces the alteration of peptides presented by HLA-B*15:02.

Simper, G. S., Ho, G. G. T., Celik, A. A., Huyton, T., Kuhn, J., Kunze-Schumacher, H., et al. (2018). Carbamazepine-mediated adverse drug reactions: CBZ-10,11-epoxide but not carbamazepine induces the alteration of peptides presented by HLA-B*15:02. Journal of Immunology Research, 2018: 5086503. doi:10.1155/2018/5086503.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0002-50D7-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-B9B7-E
Genre: Journal Article

Files

show Files
hide Files
:
3002355.pdf (Publisher version), 5MB
Name:
3002355.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
:
3002355_Suppl.docx (Supplementary material), 203KB
Name:
3002355_Suppl.docx
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.wordprocessingml.document / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Simper, G. S., Author
Ho, G. G. T., Author
Celik, A. A., Author
Huyton, T.1, Author              
Kuhn, J., Author
Kunze-Schumacher, H., Author
Blasczyk, R., Author
Bade-Döding, C., Author
Affiliations:
1Department of Cellular Logistics, MPI for Biophysical Chemistry, Max Planck Society, ou_578574              

Content

show
hide
Free keywords: -
 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*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*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*15:02 heavy chain; however, solely EPX altered the peptide-binding motif of B*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.

Details

show
hide
Language(s): eng - English
 Dates: 2018-09-13
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1155/2018/5086503
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Immunology Research
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 12 Volume / Issue: 2018 Sequence Number: 5086503 Start / End Page: - Identifier: -