JID innovations : skin science from molecules to population health最新文献

{"title":"Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis","authors":"Stefano G. Daniele ,&nbsp;Sherif A. Eldirany ,&nbsp;Giovanni Damiani ,&nbsp;Minh Ho ,&nbsp;Christopher G. Bunick","doi":"10.1016/j.xjidi.2024.100261","DOIUrl":"10.1016/j.xjidi.2024.100261","url":null,"abstract":"<div><p>IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40; however, the structural composition of the IL-23–binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and K_D and k_off but not k_on. Epitope surface area, K_D, and k_off were further associated with short-term (10–16 weeks) and long-term (44–60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, k_on, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000079/pdfft?md5=7ef11109ecf7af14c9c15048e351d873&pid=1-s2.0-S2667026724000079-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139537731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting Report: Highlights of 12th World Congress of Itch","authors":"Sarah G. Brooks ,&nbsp;Rami H. Mahmoud ,&nbsp;Gil Yosipovitch","doi":"10.1016/j.xjidi.2023.100254","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100254","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100254"},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000814/pdfft?md5=8ad303cb08d64d8043a713efdc5c5011&pid=1-s2.0-S2667026723000814-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generative Artificial Intelligence, Large Language Models, and JID Innovations","authors":"Russell P. Hall III (Editor, JID Innovations)","doi":"10.1016/j.xjidi.2024.100256","DOIUrl":"10.1016/j.xjidi.2024.100256","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100256"},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000018/pdfft?md5=3c2b4dd626f753193551095c43074471&pid=1-s2.0-S2667026724000018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bispecific, Tetravalent Antibody Targeting Inflammatory and Pruritogenic Pathways in Atopic Dermatitis","authors":"Julia Tietz ,&nbsp;Tea Gunde ,&nbsp;Stefan Warmuth ,&nbsp;Christopher Weinert ,&nbsp;Matthias Brock ,&nbsp;Alexandre Simonin ,&nbsp;Christian Hess ,&nbsp;Maria Johansson ,&nbsp;Fabio Spiga ,&nbsp;Simone Muntwiler ,&nbsp;Belinda Wickihalder ,&nbsp;Dana Mahler ,&nbsp;Dania Diem ,&nbsp;Julia Zeberer ,&nbsp;Robin Heiz ,&nbsp;Naomi Flückiger ,&nbsp;Noriko Shiraishi ,&nbsp;Yoshihide Miyake ,&nbsp;Nobuaki Takahashi ,&nbsp;Markus Fehrholz ,&nbsp;Daniel Snell","doi":"10.1016/j.xjidi.2024.100258","DOIUrl":"10.1016/j.xjidi.2024.100258","url":null,"abstract":"<div><p>Inhibition of IL-4/IL-13 signaling has dramatically improved the treatment of atopic dermatitis (AD). However, in many patients, clinical responses are slow to develop and remain modest. Indeed, some symptoms of AD are dependent on IL-31, which is only partially reduced by IL-4/IL-13 inhibition. Thus, there is an unmet need for AD treatments that concomitantly block IL-4/IL-13 and IL-31 pathways. We engineered NM26-2198, a bispecific tetravalent antibody designed to accomplish this task. In reporter cell lines, NM26-2198 concomitantly inhibited IL-4/IL-13 and IL-31 signaling with a potency comparable with that of the combination of an anti–IL-4Rα antibody (dupilumab) and an anti–IL-31 antibody (BMS-981164). In human PBMCs, NM26-2198 inhibited IL-4–induced upregulation of CD23, demonstrating functional binding to FcγRII (CD32). NM26-2198 also inhibited the secretion of the AD biomarker thymus and activation-regulated chemokine (TARC) in blood samples from healthy human donors. In male cynomolgus monkeys, NM26-2198 exhibited favorable pharmacokinetics and significantly inhibited IL-31–induced scratching at a dose of 30 mg/kg. In a repeat-dose, good laboratory practice toxicology study in cynomolgus monkeys, no adverse effects of NM26-2198 were observed at a weekly dose of 125 mg/kg. Together, these results justify the clinical investigation of NM26-2198 as a treatment for moderate-to-severe AD.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100258"},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000043/pdfft?md5=2f04d58000317f1b35b83dcef9c6e90d&pid=1-s2.0-S2667026724000043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139538703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Responsible but Innovative Use of Artificial Intelligence in Scientific Publishing","authors":"Trevor Champagne ,&nbsp;Neil Shear","doi":"10.1016/j.xjidi.2024.100257","DOIUrl":"10.1016/j.xjidi.2024.100257","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100257"},"PeriodicalIF":0.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400002X/pdfft?md5=fdd74f3438343feaf3a4c72d50b3fec7&pid=1-s2.0-S266702672400002X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade","authors":"Sally E. Dickinson ,&nbsp;Prajakta Vaishampayan ,&nbsp;Jana Jandova ,&nbsp;Yuchen (Ella) Ai ,&nbsp;Viktoria Kirschnerova ,&nbsp;Tianshun Zhang ,&nbsp;Valerie Calvert ,&nbsp;Emanuel Petricoin III ,&nbsp;H-H. Sherry Chow ,&nbsp;Chengcheng Hu ,&nbsp;Denise Roe ,&nbsp;Ann Bode ,&nbsp;Clara Curiel-Lewandrowski ,&nbsp;Georg T. Wondrak","doi":"10.1016/j.xjidi.2023.100255","DOIUrl":"10.1016/j.xjidi.2023.100255","url":null,"abstract":"<div><p>The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light–induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma. Topical application of the small-molecule PD-L1 inhibitor BMS-202 significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin, also confirmed in human HaCaT reporter keratinocytes. RT-qPCR analysis revealed that BMS-202 antagonized UV induction of inflammatory gene expression. Likewise, UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202. NanoString nCounter transcriptomic analysis confirmed downregulation of cutaneous innate immunity- and inflammation-related responses, together with upregulation of immune response pathway gene expression. Further mechanistic analysis confirmed that BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. These data suggest that topical pharmacological PD-L1 antagonism using BMS-202 shows promise for skin protection against photodamage.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000826/pdfft?md5=3d07b8adc86d48e1b946287656546618&pid=1-s2.0-S2667026723000826-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139392996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Aggregation of Microbiome Sequencing Data Provides Insights into the Associations between the Skin Microbiome and Psoriasis","authors":"Alfred A. Chan ,&nbsp;Patrick T. Tran ,&nbsp;Delphine J. Lee","doi":"10.1016/j.xjidi.2023.100249","DOIUrl":"10.1016/j.xjidi.2023.100249","url":null,"abstract":"<div><p>Although prior studies have reported distinct skin microbiome profiles associated with psoriasis, differences in methods and analyses limit generalizable conclusions. Individual studies have actually reported conflicting findings; for example, <em>Propionibacterium</em> and <em>Staphylococcus</em> have been significantly associated with both psoriatic lesions and healthy skin. Qualitative reviews have attempted to summarize this body of work, but there is great variability across the studies’ findings and methods. To better unify these data, we created a meta-analysis of all publicly available datasets by utilizing a uniform bioinformatics pipeline and reference database to investigate associations of the skin microbiome in psoriasis. A total of 977 skin swab samples (341 lesional, 295 nonlesional, and 341 healthy) from 6 studies were analyzed. The aggregated analysis revealed a higher relative abundance of microorganisms, including <em>Staphylococcus aureus</em> and <em>Corynebacterium simulans</em>, among others, from patients with psoriasis than those from healthy swab samples; in addition, <em>Cutibacterium acnes</em>, <em>Lawsonella</em> unclassified, and <em>S warneri</em> were significantly higher in healthy samples. Furthermore, comparison of functional pathways predicted from 16S gene markers showed that L-ornithine biosynthesis and L-histidine biosynthesis were lower in psoriatic lesions than in healthy controls. Taken together, this meta-analysis allows for a more generalizable association between the skin microbiome and psoriasis.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100249"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000759/pdfft?md5=0c5b21ff705bf319bd785892407f9163&pid=1-s2.0-S2667026723000759-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139299087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Portable System for In-Clinic Differentiation of Skin Cancers from Benign Skin Lesions and Inflammatory Dermatoses","authors":"Michel Nieuwoudt ,&nbsp;Paul Jarrett ,&nbsp;Hannah Matthews ,&nbsp;Michelle Locke ,&nbsp;Marco Bonesi ,&nbsp;Brydon Burnett ,&nbsp;Hannah Holtkamp ,&nbsp;Claude Aguergaray ,&nbsp;Ira Mautner ,&nbsp;Thom Minnee ,&nbsp;M. Cather Simpson","doi":"10.1016/j.xjidi.2023.100238","DOIUrl":"10.1016/j.xjidi.2023.100238","url":null,"abstract":"<div><p>The exquisite sensitivity of Raman spectroscopy for detecting biomolecular changes in skin cancer has previously been explored; however, this mostly required analysis of excised tissue samples using bulky, immobile laboratory instrumentation. In this study, the technique was translated for clinical use with a portable Raman system and customized fiber optic probe and applied to differentiation of skin cancers from benign lesions and inflammatory dermatoses. The aim was to provide an easy-to-use, easy-to-manage assessment tool for clinicians to use in their daily patient examination routine to perform rapid Raman measurements of skin lesions in vivo. Using this system, &gt;867 spectra were measured in vivo from 330 patients with a wide variety of different benign skin lesions (n = 603), inflammatory dermatoses (n = 140), and skin cancers (n = 124). Ethnicities represented were 70% European; 16% Asian; 6% Māori; 5% Pacific people; and 4% Middle East, Latin American, and African. Accurate differentiation of skin cancers from benign lesions and inflammatory dermatoses was achieved using partial least squares discriminant analysis, with area under curve for the receiver operator curves for external validation sets ranging from 0.916 to 0.958. This study shows evidence for robust clinical translation of Raman spectroscopy for rapid, accurate diagnosis of skin cancer.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100238"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000644/pdfft?md5=27035fe51a51ec08108ee2d135bb69b9&pid=1-s2.0-S2667026723000644-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134994567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-Based Communication to Increase Melanoma Knowledge and Skin Checks","authors":"Ariel Nadratowski ,&nbsp;Brittany Shoots-Reinhard ,&nbsp;Autumn Shafer ,&nbsp;Jerusha Detweiler-Bedell ,&nbsp;Brian Detweiler-Bedell ,&nbsp;Sancy Leachman ,&nbsp;Ellen Peters","doi":"10.1016/j.xjidi.2023.100253","DOIUrl":"10.1016/j.xjidi.2023.100253","url":null,"abstract":"<div><p>Rates of melanoma—the deadliest form of skin cancer—have increased. Early detection can save lives, and patients have a critical role to play in checking their skin. We aim to identify health communication messages that best educate the public and increase intentions toward skin checks. After viewing messages intended to increase melanoma knowledge, participants correctly identified a greater proportion (74.6 vs 70.4%) of moles (mean number = 17.9, 95% confidence interval [CI] = 17.5–18.3 vs 16.9, 95% CI = 16.6–17.3; <em>P</em> &lt; .001, partial eta-squared = 0.03) and had knowledge of more melanoma warning signs (mean number = 5.8, 95% CI = 5.7–5.8 vs 5.6, 95% CI = 5.5–5.7, <em>P</em> = .01, partial eta-squared = 0.02). After viewing messages intended to increase self-confidence in checking their skin accurately, they were also more likely to report greater intentions to do a skin check on a scale of 1–5 (mean number = 3.8, 95% CI = 3.7–3.9 vs 3.6, 95% CI = 3.4–3.7, <em>P</em> = .005, partial eta-squared = 0.02). Online melanoma messages aimed at increasing both melanoma knowledge and skin-check confidence may be most effective in improving the accuracy of skin self-examinations and intentions to do them.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100253"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000796/pdfft?md5=118f40cd536db7b24ec4a6b4ddd14f1e&pid=1-s2.0-S2667026723000796-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139192774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Fibroinflammatory and Fibrotic Transcriptomic Subsets of Human Cutaneous Sclerotic Chronic Graft-Versus-Host Disease","authors":"Rachel K. Rosenstein ,&nbsp;Jeremy J. Rose ,&nbsp;Stephen R. Brooks ,&nbsp;Wanxia L. Tsai ,&nbsp;Massimo Gadina ,&nbsp;Steven Z. Pavletic ,&nbsp;Keisuke Nagao ,&nbsp;Edward W. Cowen","doi":"10.1016/j.xjidi.2023.100246","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100246","url":null,"abstract":"<div><p>Cutaneous sclerotic chronic graft-versus-host disease (cGVHD) is a common and highly morbid complication of allogeneic hematopoietic stem cell transplantation. Our goals were to identify signals active in the skin of patients with sclerotic cGVHD in an effort to better understand how to treat this manifestation and to explore the heterogeneity of the disease. We identified genes that are significantly upregulated in the skin of patients with sclerotic cGVHD (n = 17) compared with those in the skin of patients who underwent allogeneic hematopoietic stem cell transplantation without cutaneous cGVHD (n = 9) by bulk RNA sequencing. Sclerotic cGVHD was most associated with T helper 1, phagocytic, and fibrotic pathways. In addition, different transcriptomic groups of affected patients were discovered: those with fibrotic and inflammatory/T helper 1 gene expression (the fibroinflammatory group) and those with predominantly fibrotic/TGFβ-associated expression (the fibrotic group). Further study will help elucidate whether these gene expression findings can be used to tailor treatment decisions. Multiple proteins encoded by highly induced genes in the skin (<em>SFRP4</em>, <em>SERPINE2</em>, <em>COMP</em>) were also highly induced in the plasma of patients with sclerotic cGVHD (n = 16) compared with those in plasma of control patients who underwent allogeneic hematopoietic stem cell transplantation without sclerotic cGVHD (n = 17), suggesting these TGFβ and Wnt pathway mediators as candidate blood biomarkers of the disease.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100246"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000723/pdfft?md5=3de50b8cb7956c47138b20eda621217a&pid=1-s2.0-S2667026723000723-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}