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HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.

Publication ,  Journal Article
Yang, C-WO; Hung, S-I; Juo, C-G; Lin, Y-P; Fang, W-H; Lu, I-H; Chen, S-T; Chen, Y-T
Published in: J Allergy Clin Immunol
October 2007

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can involve MHC-restricted presentation of a drug or its metabolites for T-cell activation. HLA-B(*)1502 tightly associated with carbamazepine (CBZ) induced these conditions in a Han Chinese population. OBJECTIVE: We sought to identify HLA-B(*)1502-bound peptides that might be involved in CBZ-induced SJS/TEN. METHODS: Soluble HLA-B(*)1502 was used to identify bound peptides in the presence and absence of CBZ by using liquid chromatography-tandem mass spectrometry. Peptide-binding assays were performed to detect the specific interaction between the HLA molecule and the identified peptides. Mass spectra were compared to detect CBZ-modified peptides. RESULTS: We identified more than 145 peptides bound to HLA-B(*)1502. In 13 of 15 peptides examined, we functionally confirmed their specificity with binding assays. Preferable uses of these peptides at the anchoring residues P2 and P9 were similar to those observed in other HLA-B alleles in the Han Chinese population. However, the preferable use of serine residues at the nonanchoring position (P) 5, P6, P7, and P8 appeared to be unique for the B(*)1502 peptides. No specific CBZ-modified peptides were detected when we compared the mass spectra of peptides detected in the presence or absence of the drug. CONCLUSION: Noncovalent interaction between a drug and an HLA complex might contribute to cytotoxic T cell-mediated cell death in patients with SJS/TEN. CLINICAL IMPLICATIONS: An understanding of pharmacologic interaction of drugs with an HLA complex might lead to safer drugs that avoid SJS/TEN.

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Published In

J Allergy Clin Immunol

DOI

ISSN

0091-6749

Publication Date

October 2007

Volume

120

Issue

4

Start / End Page

870 / 877

Location

United States

Related Subject Headings

  • Stevens-Johnson Syndrome
  • Peptides
  • Mass Spectrometry
  • Humans
  • HLA-B Antigens
  • Carbamazepine
  • Allergy
  • 3204 Immunology
  • 1107 Immunology
 

Citation

APA
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ICMJE
MLA
NLM
Yang, C.-W., Hung, S.-I., Juo, C.-G., Lin, Y.-P., Fang, W.-H., Lu, I.-H., … Chen, Y.-T. (2007). HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol, 120(4), 870–877. https://doi.org/10.1016/j.jaci.2007.06.017
Yang, Chih-Wen Ou, Shuen-Iu Hung, Chiun-Gung Juo, Ya-Ping Lin, Wu-Hsiang Fang, I-Hsuan Lu, Shui-Tein Chen, and Yuan-Tsong Chen. “HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.J Allergy Clin Immunol 120, no. 4 (October 2007): 870–77. https://doi.org/10.1016/j.jaci.2007.06.017.
Yang C-WO, Hung S-I, Juo C-G, Lin Y-P, Fang W-H, Lu I-H, et al. HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol. 2007 Oct;120(4):870–7.
Yang, Chih-Wen Ou, et al. “HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.J Allergy Clin Immunol, vol. 120, no. 4, Oct. 2007, pp. 870–77. Pubmed, doi:10.1016/j.jaci.2007.06.017.
Yang C-WO, Hung S-I, Juo C-G, Lin Y-P, Fang W-H, Lu I-H, Chen S-T, Chen Y-T. HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol. 2007 Oct;120(4):870–877.
Journal cover image

Published In

J Allergy Clin Immunol

DOI

ISSN

0091-6749

Publication Date

October 2007

Volume

120

Issue

4

Start / End Page

870 / 877

Location

United States

Related Subject Headings

  • Stevens-Johnson Syndrome
  • Peptides
  • Mass Spectrometry
  • Humans
  • HLA-B Antigens
  • Carbamazepine
  • Allergy
  • 3204 Immunology
  • 1107 Immunology