PMID- 35526384 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20220623 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 109 DP - 2022 Aug TI - Carbamazepine-modified HLA-A*24:02-bound peptidome: Implication of CORO1A in skin rash. PG - 108804 LID - S1567-5769(22)00288-0 [pii] LID - 10.1016/j.intimp.2022.108804 [doi] AB - 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 POmega, 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. CI - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Min, Fuli AU - Min F AD - Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China. FAU - Fan, Cuixia AU - Fan C AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China. FAU - Zeng, Yuanjin AU - Zeng Y AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China. FAU - He, Na AU - He N AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China. FAU - Zeng, Tao AU - Zeng T AD - Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China. FAU - Qin, Bing AU - Qin B AD - Epilepsy Center and Department of Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China. Electronic address: qinbing900@jnu.edu.cn. FAU - Shi, Yiwu AU - Shi Y AD - Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China. Electronic address: stoneyiwu@gzhmu.edu.cn. LA - eng PT - Journal Article DEP - 20220505 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anticonvulsants) RN - 0 (HLA-A*24:02 antigen) RN - 0 (HLA-A24 Antigen) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B*15:02 antigen) RN - 0 (HLA-B15 Antigen) RN - 0 (Microfilament Proteins) RN - 0 (Peptides) RN - 145420-64-0 (coronin proteins) RN - 33CM23913M (Carbamazepine) RN - K3Z4F929H6 (Lysine) SB - IM MH - Anticonvulsants/adverse effects MH - *Carbamazepine/adverse effects MH - *Drug Hypersensitivity MH - *Exanthema/chemically induced/metabolism MH - Genetic Predisposition to Disease MH - HLA-A24 Antigen/genetics MH - HLA-B Antigens/genetics MH - HLA-B15 Antigen MH - Humans MH - Lysine MH - *Microfilament Proteins MH - Peptides/genetics/metabolism MH - *Stevens-Johnson Syndrome/genetics OTO - NOTNLM OT - Carbamazepine, lamotrigine, HLA-A*24:02 OT - Coronin 1A OT - Skin rash EDAT- 2022/05/09 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/05/08 18:10 PHST- 2022/01/23 00:00 [received] PHST- 2022/04/01 00:00 [revised] PHST- 2022/04/24 00:00 [accepted] PHST- 2022/05/09 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/05/08 18:10 [entrez] AID - S1567-5769(22)00288-0 [pii] AID - 10.1016/j.intimp.2022.108804 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Aug;109:108804. doi: 10.1016/j.intimp.2022.108804. Epub 2022 May 5.