Zhang, Yuan, Grice, Sophie, Wang, Na, Liu, Yongxia, Zhao, Qing, Liu, Tingting, Sun, Lele, Mi, Zihao, Wang, Jianwen, Yu, Gongqi et al (show 6 more authors)
(2023)
HLA-C*15:02 and epidermal growth factor receptor inhibitor-induced erosive pustular dermatosis of the scalp.
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 48 (11).
pp. 1260-1265.
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HLA C1502 and epidermal growth factor receptor inhibitor induced erosive pustular dermatosis of the scalp..pdf - Open Access published version Download (1MB) | Preview |
Abstract
Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs. The pathogenesis of EGFRI-induced EPDS is poorly understood. Here we present three cases of EPDS induced by EGFRIs. The proteins LTA4H (leukotriene A-4 hydrolase), METAP1 (methionine aminopeptidase 1), BID (BH3-interacting domain death agonist), SMAD1 (mothers against decapentaplegic homologue), PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A), YES1 (tyrosine-protein kinase Yes) and EGFL7 (epidermal growth factor-like protein 7) were significantly upregulated in EGFRI-stimulated peripheral blood mononuclear cell cultures, and validated in the lesions. All of the proteins colocalized with CD4+ and CD8+ T-cell expression. Next-generation-based human leucocyte antigen (HLA) typing showed all patients carried HLA-C*15:02, and modelling studies showed that afatinib and erlotinib bound well within the E/F binding pockets of HLA-C*15:02. Moreover, T cells were preferentially activated by EGFRIs in individuals carrying HLA-C*15:02. The case series revealed that EGFRI-induced EPDS may be mediated by drug-specific T cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Scalp, Leukocytes, Mononuclear, Humans, Skin Diseases, Exanthema, Aminopeptidases, Calcium-Binding Proteins, HLA-C Antigens, EGF Family of Proteins, ErbB Receptors |
| Divisions: | Faculty of Health and Life Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Sep 2023 10:53 |
| Last Modified: | 28 Oct 2023 16:38 |
| DOI: | 10.1093/ced/llad282 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3172851 |
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