Myriam Cassagne , Stéphane Galiacy , Anna Kychygina , Eric Chapotot , Martin Wallaert , Bertrand Vabres , Marie Tauber , Sébastien Barbarot , Carle Paul , Pierre Fournié , Michel Simon , FRench Atopic DErmatitis Network and the Groupe de Recherche sur l'Eczema Atopique
{"title":"经杜比鲁单抗治疗的特应性皮炎患者的浅层结膜细胞显示出牛皮癣转录组特征","authors":"Myriam Cassagne , Stéphane Galiacy , Anna Kychygina , Eric Chapotot , Martin Wallaert , Bertrand Vabres , Marie Tauber , Sébastien Barbarot , Carle Paul , Pierre Fournié , Michel Simon , FRench Atopic DErmatitis Network and the Groupe de Recherche sur l'Eczema Atopique","doi":"10.1016/j.jid.2024.08.024","DOIUrl":null,"url":null,"abstract":"<div><div>Dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. However, a subset of patients experiences ocular adverse events (OAEs), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of conjunctival cells of patients with atopic dermatitis collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in 2 groups according to their ophthalmological status at M4: 12 with OAEs (OAE+) and 24 without (OAE−). The analysis revealed 52 differentially expressed genes between OAE+ and OAE− patients at M0 and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. In addition, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 differentially expressed genes selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ versus OAE− patients, validating the psoriasis signature, whereas <em>MUC7</em> was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some patients with atopic dermatitis to developing OAEs upon dupilumab treatment.</div></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"145 5","pages":"Pages 1050-1059.e6"},"PeriodicalIF":5.7000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Superficial Conjunctival Cells from Dupilumab-Treated Patients with Atopic Dermatitis with Ocular Adverse Events Display a Transcriptomic Psoriasis Signature\",\"authors\":\"Myriam Cassagne , Stéphane Galiacy , Anna Kychygina , Eric Chapotot , Martin Wallaert , Bertrand Vabres , Marie Tauber , Sébastien Barbarot , Carle Paul , Pierre Fournié , Michel Simon , FRench Atopic DErmatitis Network and the Groupe de Recherche sur l'Eczema Atopique\",\"doi\":\"10.1016/j.jid.2024.08.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. However, a subset of patients experiences ocular adverse events (OAEs), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of conjunctival cells of patients with atopic dermatitis collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in 2 groups according to their ophthalmological status at M4: 12 with OAEs (OAE+) and 24 without (OAE−). The analysis revealed 52 differentially expressed genes between OAE+ and OAE− patients at M0 and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. In addition, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 differentially expressed genes selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ versus OAE− patients, validating the psoriasis signature, whereas <em>MUC7</em> was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some patients with atopic dermatitis to developing OAEs upon dupilumab treatment.</div></div>\",\"PeriodicalId\":16311,\"journal\":{\"name\":\"Journal of Investigative Dermatology\",\"volume\":\"145 5\",\"pages\":\"Pages 1050-1059.e6\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Investigative Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022202X2402102X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Investigative Dermatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022202X2402102X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Superficial Conjunctival Cells from Dupilumab-Treated Patients with Atopic Dermatitis with Ocular Adverse Events Display a Transcriptomic Psoriasis Signature
Dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. However, a subset of patients experiences ocular adverse events (OAEs), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of conjunctival cells of patients with atopic dermatitis collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in 2 groups according to their ophthalmological status at M4: 12 with OAEs (OAE+) and 24 without (OAE−). The analysis revealed 52 differentially expressed genes between OAE+ and OAE− patients at M0 and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. In addition, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 differentially expressed genes selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ versus OAE− patients, validating the psoriasis signature, whereas MUC7 was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some patients with atopic dermatitis to developing OAEs upon dupilumab treatment.
期刊介绍:
Journal of Investigative Dermatology (JID) publishes reports describing original research on all aspects of cutaneous biology and skin disease. Topics include biochemistry, biophysics, carcinogenesis, cell regulation, clinical research, development, embryology, epidemiology and other population-based research, extracellular matrix, genetics, immunology, melanocyte biology, microbiology, molecular and cell biology, pathology, percutaneous absorption, pharmacology, photobiology, physiology, skin structure, and wound healing