Journal of dermatological science最新文献

{"title":"Risankizumab differentially modulates circulating T-cell populations in psoriasis according to autoreactivity status.","authors":"Rebecca Favaro, Paola Facheris, Alessandra Formai, Luigi Gargiulo, Luciano Ibba, Giovanni Fiorillo, Roberta Valeria Latorre, Jessica Avagliano, Alessandra Narcisi, Giampiero Girolomoni, Santo Raffaele Mercuri, Antonio Costanzo","doi":"10.1016/j.jdermsci.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.08.002","url":null,"abstract":"<p><strong>Background: </strong>In a recent paper, our group described that the presence of double autoreactivity to both LL37 and ADAMTSL5 autoantigens in psoriatic patients decreased the clinical responses to risankizumab, but how this influences the changes in the peripheral inflammatory T-cell populations is still unknown.</p><p><strong>Objective: </strong>This study aims to evaluate how risankizumab modulates the circulating inflammatory T-cell populations in psoriatic patients and, specifically, in autoreactive subjects.</p><p><strong>Methods: </strong>The presence of LL37- and ADAMTSL5-reactive circulating T-cells was assessed in a cohort of 142 psoriatic patients, and 87 demonstrated autoreactivity at baseline. Patients were treated with risankizumab for 52 weeks, and specific T-cell populations were analyzed at different timepoints.</p><p><strong>Results: </strong>The frequency of Ki67⁺CD4⁺, Ki67⁺CD8⁺ T-cells, CD8⁺IL-17⁺ and CD8⁺IL-22⁺ T-cells showed a positive correlation with baseline PASI and decreased with treatment. Notably, CD8⁺IL-17⁺ T-cells decreased both in single-LL37 and single-ADAMTSL5-reactive subjects, but not in subjects that showed autoreactivity to both autoantigens. LL37 autoreactivity of CD4⁺ and CD8⁺ T-cells decreased with treatment, but not for CD4⁺ in double-reactive subjects. While Treg frequency negatively correlated with baseline PASI and increased within 16 weeks of treatment, significantly decreasing the IL-17⁺CD4⁺/Treg ratio over time, Treg modulation was not evident in double-reactive subjects. Interestingly, the subpopulations of CD8⁺MAIT IL-17⁺ and CD3⁺MAIT IL-22⁺ cells, involved also in psoriatic arthritis, decreased in treated subjects following IL-23 inhibition.</p><p><strong>Conclusion: </strong>Rizankizumab efficiently decreases the circulating inflammatory T-cell populations and modulates Tregs' plasticity in single-LL37- or single-ADAMTSL5-reactive subjects, but not in double-reactive subjects.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Granzyme K contributes to acute itch in psoriasis.","authors":"Aoi Hiroyasu, Beni Amatya, Daisuke Tsuruta, David J Granville, Sho Hiroyasu","doi":"10.1016/j.jdermsci.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.08.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of FOXA1 and ERBB2 activating mutations in extramammary Paget's disease: A retrospective multicenter analysis of 99 cases from Japanese and Taiwanese cohorts.","authors":"Michiya Omi, Takuya Takeichi, Yusuke Okuno, Chao-Kai Hsu, Cheng-Lin Wu, Yi-Han Chang, Shoichiro Mori, Yuta Yamashita, Akira Miyazaki, Takaya Taira, Teruki Yanagi, Keitaro Fukuda, Tatsuhiro Noda, Yuika Suzuki, Yoshinao Muro, Masashi Akiyama","doi":"10.1016/j.jdermsci.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.08.001","url":null,"abstract":"<p><strong>Background: </strong>Extramammary Paget's disease (EMPD) occurs in areas where apocrine glands are abundant. EMPD is associated with the known somatic hotspot mutation g.chr14:38064406 G>A in the promoter region of FOXA1 and S310F in ERBB2. Whether EMPD patients in non-Japanese populations have FOXA1 driver mutations remains undetermined, and the relationship between the clinical characteristics of EMPD patients and the presence of somatic FOXA1 driver mutations has yet to be investigated.</p><p><strong>Objective: </strong>To assess the prevalence and clinical significance of the FOXA1 and ERBB2 hotspot somatic mutations.</p><p><strong>Methods: </strong>Surgical specimens from 99 EMPD patients who underwent surgery from January 2013 to March 2024 were collected from five facilities in Japan and Taiwan. To detect the somatic mutations, amplicon sequencing was performed for FOXA1, and ddPCR was conducted for ERBB2. Immunohistochemical analysis for FOXA1 was performed on 38 samples.</p><p><strong>Results: </strong>The frequencies of the FOXA1 (g.chr14:38064406 G>A) mutation and the ERBB2 S310F mutation were 8/93 (8.6 %) and 37/93 (40.0 %), respectively, among the non-fresh-frozen specimens. FOXA1 somatic hotspot mutation-positive cases were found at all five medical institutions. Regardless of the mutational status of the FOXA1 promoter mutation, all examined cases immunohistochemically exhibited strong FOXA1 expression in the Paget cell nuclei. No significant correlation was found between the FOXA1 somatic mutation or the ERBB2 somatic mutation and any clinical parameter.</p><p><strong>Conclusion: </strong>The FOXA1 somatic hotspot mutation was found in both Japanese and Taiwanese EMPD patients. We cannot rule out the possibility that FOXA1 might be a potential target for EMPD therapies in Japan and Taiwan.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel ATP2C1 genetic variants in a Dutch cohort of patients with Hailey-Hailey disease.","authors":"Marie-Eline P H Debeuf, Valerie L R M Verstraeten, Peter C van den Akker, Ruud G L Nellen, Henny H Lemmink, Antoni H Gostyński, Peter M Steijlen, Marieke C Bolling, Michel van Geel","doi":"10.1016/j.jdermsci.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.07.004","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast cells express IL17A, IL17F and RORC in lesional psoriatic skin, are activated before therapy and persist in high numbers in a resting state with IL-17A positivity after treatment","authors":"Theresa Benezeder ,&nbsp;Natalie Bordag ,&nbsp;Johannes Woltsche ,&nbsp;Andrea Teufelberger ,&nbsp;Isabella Perchthaler ,&nbsp;Wolfgang Weger ,&nbsp;Wolfgang Salmhofer ,&nbsp;Alexandra Gruber-Wackernagel ,&nbsp;Clemens Painsi ,&nbsp;Qian Zhan ,&nbsp;Amin El-Heliebi ,&nbsp;Magda Babina ,&nbsp;Rachael Clark ,&nbsp;Peter Wolf","doi":"10.1016/j.jdermsci.2025.05.006","DOIUrl":"10.1016/j.jdermsci.2025.05.006","url":null,"abstract":"<div><h3>Background</h3><div>The proinflammatory cytokine IL-17 is known to play an important role in psoriasis pathogenesis, but little is known about its regulation in psoriasis or after treatment.</div></div><div><h3>Objective</h3><div>Aiming to investigate the role of IL-17 regulation in the resolution of psoriasis, we analyzed biopsy samples from patients with plaque psoriasis, including non-lesional and lesional skin at baseline and after anti-IL-17 and -IL-23 antibody, topical dithranol or UVB treatment as well as skin from healthy donors.</div></div><div><h3>Methods</h3><div>Skin biopsy samples were analyzed using immunostaining, RNA sequencing and in situ mRNA detection. In addition, we investigated IL-17 concentration of primary human skin mast cell supernatants after stimulation with the pro-inflammatory cytokines TNFα, IL-22, IL-23 and IFNγ.</div></div><div><h3>Results</h3><div>A high number of IL-17A+ mast cells persisted in resolved lesions after treatment and correlated inversely with the time span in remission. IL-17A+ mast cells were found in T cell-rich areas and near resident memory T cells in active and resolved lesions. CIBERSORTx deconvolution of RNA-seq data of active and dithranol-treated psoriasis lesions showed that activated mast cells were increased in psoriatic skin but returned to normal levels after treatment. Primary skin mast cells responded with an increased release of IL-17A after stimulation with the pro-inflammatory cytokines and in situ mRNA detection revealed positive signals for <em>IL17A, IL17F</em> and <em>RORC</em> in mast cells.</div></div><div><h3>Conclusion</h3><div>Thus, together with T cells, mast cells seem to be important players of the IL-23/IL17 axis underlying psoriasis pathogenesis and relevant for early disease recurrence.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Pages 53-63"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary metabolomics for skin cancer screening","authors":"Masahiro Hayashi ,&nbsp;Shigeo Ishikawa ,&nbsp;Masahiro Sugimoto ,&nbsp;Naoki Okuyama ,&nbsp;Kaoru Edamatsu ,&nbsp;Kazuyuki Yusa ,&nbsp;Tomoharu Hemmi ,&nbsp;Takayuki Konno ,&nbsp;Ken Okamura ,&nbsp;Yuta Araki ,&nbsp;Mariko Nikaido ,&nbsp;Yoriko Yaguchi ,&nbsp;Toru Saito ,&nbsp;Shoko Nakano ,&nbsp;Ami Hemmi ,&nbsp;Yutaka Hozumi ,&nbsp;Tamio Suzuki","doi":"10.1016/j.jdermsci.2025.05.003","DOIUrl":"10.1016/j.jdermsci.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div>If skin cancer (SC) can be screened using saliva, it would be extremely important for improving the prognosis of skin cancer. However, there is currently no available data on salivary screening for SC.</div></div><div><h3>Objective</h3><div>This study aimed to identify salivary metabolomic<span> biomarkers for SC screening by comparing tissue and saliva samples.</span></div></div><div><h3>Methods</h3><div>This single-center study involved SC patients from Yamagata University Hospital, enrolled between May 2017 and April 2020. For the healthy controls (HCs), our database comprising salivary metabolomics data of HCs was used. Whole unstimulated saliva samples were collected from patients with SC (n = 75) and HCs (n = 77). Paired tumor and control tissues after SC resection were obtained from the same patients who donated saliva. Hydrophilic metabolites in the tissue and saliva samples were comprehensively analyzed using capillary electrophoresis–mass spectrometry. Using these candidate metabolites, a multiple logistic regression (MLR) model was developed to differentiate SC from HCs</div></div><div><h3>Results</h3><div>Sixty-six and 12 metabolites showed significant differences in tissues and saliva, respectively. Of these, six metabolites were commonly different between SC and HCs. Spermidine<span><span><span>, 2-aminobutyric acid, and isoleucine were selected to develop the MLR model. The model exhibited a large area under the receiver operating characteristic curve (0.802, 95 % confidence interval: 0.731–0.874, P &lt; 0.0001). Additionally, no significant differences were shown in candidate salivary metabolites between stages in both </span>malignant melanoma and </span>squamous cell carcinoma.</span></div></div><div><h3>Conclusions</h3><div>The salivary metabolomic profiles between SC and HCs differed clearly. This combination of salivary metabolites could serve as non-invasive biomarkers for screening SC.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Pages 90-96"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-read sequencing cracks unsolved cases and further improves genome diagnostics in epidermolysis bullosa","authors":"Eddy N. de Boer ,&nbsp;L. Agnes Grutters ,&nbsp;Rosalie Baardman ,&nbsp;Daniëlle Schoonhoven ,&nbsp;Jeroen Bremer ,&nbsp;Rindert R. Venema ,&nbsp;Femke Boorsma ,&nbsp;Jelkje J. de Boer-Bergsma ,&nbsp;Gilles F.H. Diercks ,&nbsp;Henny H. Lemmink ,&nbsp;Sabrina Z. Commandeur-Jan ,&nbsp;Dorieke. J. Dijkstra ,&nbsp;Lennart F. Johansson ,&nbsp;Marieke C. Bolling ,&nbsp;Cleo C. van Diemen ,&nbsp;Peter C. van den Akker","doi":"10.1016/j.jdermsci.2025.04.014","DOIUrl":"10.1016/j.jdermsci.2025.04.014","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Pages 97-100"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eribulin inhibits tumor growth of two novel patient-derived xenograft models of Merkel cell carcinoma","authors":"Kodai Miyamoto ,&nbsp;Teruki Yanagi ,&nbsp;Takuya Maeda ,&nbsp;Shinya Kitamura ,&nbsp;Hiroshi Nishihara ,&nbsp;Ririko Iwamoto ,&nbsp;Kenzo Takahashi ,&nbsp;Hideyuki Ujiie","doi":"10.1016/j.jdermsci.2025.05.007","DOIUrl":"10.1016/j.jdermsci.2025.05.007","url":null,"abstract":"<div><h3>Background</h3><div><span><span>Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis in advanced cases. Despite reported sensitivities to chemotherapy and </span>immunotherapy, response rates remain limited to approximately 50 % of cases. Although developing novel therapeutic strategies against MCC has been desired, few preclinical models, including cell lines and patient-derived </span>xenografts (PDXs), are available.</div></div><div><h3>Objectives</h3><div>This study aimed to establish novel preclinical research models and develop novel therapeutic strategies for MCC.</div></div><div><h3>Methods</h3><div>We analyzed 19 clinical MCC samples in our department. Moreover, to establish novel PDX tumors, we transplanted MCC tissues from Japanese patients into immunodeficient NOD/SCID mice.</div></div><div><h3>Results</h3><div><span>Histopathological analyses of 19 clinical MCC samples in our department revealed the tumors to either be infected with the Merkel cell polyomavirus<span> or have lost the expression of tumor suppressors (tumor protein p53 [p53] or RB transcriptional corepressor 1 [Rb1]). To establish novel PDX tumors, we transplanted MCC tissues from Japanese patients into immunodeficient NOD/SCID mice. Two MCC-PDX tumors were successfully implanted (MCC-PDX-MK1 and -MK2), and their histopathological and genetic characteristics were consistent with those of the original tumor. As in vivo preclinical treatments, we administered cisplatin<span>, etoposide<span>, docetaxel, or </span></span></span></span>eribulin<span> to the NOD/SCID mice. Eribulin showed antitumor activity in both MCC-PDX models.</span></div></div><div><h3>Conclusion</h3><div>Two MCC-PDX models were established successfully, and therapeutic experiments suggest that eribulin could inhibit MCC tumor growth.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Pages 82-89"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editors choice","authors":"","doi":"10.1016/S0923-1811(25)00135-5","DOIUrl":"10.1016/S0923-1811(25)00135-5","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Page ii"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A deep intronic founder variant in the SERPINB7 gene causing aberrant splicing is a potential therapeutic target for Nagashima-type palmoplantar keratoderma","authors":"Yuqi Chen ,&nbsp;Zhiming Chen ,&nbsp;Siyuan Li ,&nbsp;Juan Liu ,&nbsp;Yihe Liu ,&nbsp;Qingyue Fu ,&nbsp;Wenbo Bu ,&nbsp;Shuya Sun ,&nbsp;Tianxiao Li ,&nbsp;Ruiyu Xiang ,&nbsp;Zhongya Song ,&nbsp;Ran Mo ,&nbsp;Yong Yang","doi":"10.1016/j.jdermsci.2025.05.004","DOIUrl":"10.1016/j.jdermsci.2025.05.004","url":null,"abstract":"<div><h3>Background</h3><div><span>Nagashima-type palmoplantar keratoderma (NPPK), caused by biallelic </span><em>SERPINB7</em><span> loss-of-function variants, lacks effective treatments. Intriguingly, monoallelic exonic variants are observed in some patients with NPPK, suggesting additional genetic variants.</span></div></div><div><h3>Objective</h3><div>To characterize a deep intronic <em>SERPINB7</em><span><span> variant’s pathogenicity, elucidate its splicing dysregulation, and evaluate antisense </span>oligonucleotide (ASO) therapy.</span></div></div><div><h3>Methods</h3><div><span><span>A customized next-generation sequencing panel was applied to six Chinese NPPK patients. Pathological changes were analyzed by H&amp;E staining and immunofluorescence. </span>RNA<span> extracted from palmar skin was assessed for splicing alterations. Plasmids were generated to evaluate the expression and function of mutant SERPINB7 protein. Haplotype analysis was conducted to confirm the founder effect. RNA pull-down assays and mass spectrometry<span> were used to identify the key splicing factor. Minigene constructs were developed to characterize the splicing process </span></span></span><em>in vitro</em><span>. Finally, an ASO was designed to target this variant.</span></div></div><div><h3>Results</h3><div>A deep intronic <em>SERPINB7</em> variant was identified in six NPPK patients, leading to pseudo-exon inclusion and the production of a truncated, dysfunctional SERPINB7 protein. Haplotype analysis confirmed it as a Chinese founder variant. RNA pull-down assays revealed excessive SRSF9 binding to the abnormal transcript. <em>In vitro</em>, the ASO successfully corrected the aberrant splicing.</div></div><div><h3>Conclusion</h3><div>This study established the pathogenicity of a deep intronic founder variant in <em>SERPINB7</em> driving NPPK via SRSF9-mediated splicing dysregulation, demonstrating ASO therapeutic potential. Findings provide mechanistic insights and a targeted approach for precision therapy development for NPPK.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 2","pages":"Pages 73-81"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}