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http://purl.uniprot.org/citations/35526384http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35526384http://www.w3.org/2000/01/rdf-schema#comment"

Background

Previous studies have demonstrated that human leukocyte antigen (HLA)-A*24:02 is a common genetic risk factor for antiepileptic drug-induced skin rash, while HLA-B*15:02 is a specific risk factor for carbamazepine (CBZ)-induced Stevens Johnson syndrome and toxin epidermal necrolysis. The HLA-B*15:02 allele can alter the repertoire of endogenous peptides to trigger CBZ-induced hypersensitivity. However, it is uncertain whether HLA-A*24:02 could produce alterations in the peptide repertoire during treatment with antiepileptic drugs.

Methods

We generated stable HMy2.C1R cells expressing HLA-A*24:02 and HLA-B*15:02, clarified into 4 groups according to with or without CBZ treatment. We employed LC/MSto detect the HLA-bound peptides in 4 groups. Furthermore, we conducted in silico analysis to seek th differential expressed genes (DEGs) associated with HLA-A*24:02 and HLA-B*15:02. Finally, we verify the DEGs via qRT-PCR and Western blotting.

Results

A total of 134 peptides were identified from the four groups, mainly comprising<15 mer peptides. In CBZ-treated groups, 29 and 30 peptides showed significantly increased respectively in HLA-A*24:02 and HLA-B*15:02 positive cells comprising Lysine in PΩ, but the sources of these lysine peptides are different. Three peptides were exclusively detected in the HLA-A*24:02 positive cells treated with CBZ, of which 'SRQVVRSSK' was derived from the immune associated protein coronin 1A (CORO1A). CORO1A and its mRNA were significantly expressed in HLA-A*24:02 positive cells treated with CBZ. Additionally, this significantly high expression was identified in HLA-A*24:02 positive cells that were treated with lamotrigine (LTG). Nonetheless, CORO1A were not decreased in HLA-B*15:02 positive cells with or without CBZ or LTG treatment.

Conclusions

These findings confirmed that the alteration in the endogenous peptidome was a general mechanism of HLA-linked skin rashes and suggests that CORO1A is involved in HLA-A*24:02-associated skin rash."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.org/dc/terms/identifier"doi:10.1016/j.intimp.2022.108804"xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Fan C."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"He N."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Qin B."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Shi Y."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Zeng Y."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Zeng T."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/author"Min F."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/name"Int Immunopharmacol"xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/pages"108804"xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/title"Carbamazepine-modified HLA-A*24:02-bound peptidome: Implication of CORO1A in skin rash."xsd:string
http://purl.uniprot.org/citations/35526384http://purl.uniprot.org/core/volume"109"xsd:string
http://purl.uniprot.org/citations/35526384http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35526384
http://purl.uniprot.org/citations/35526384http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35526384
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