The Journal of investigative dermatology最新文献_第6页

Escherichia Abundance and Metabolism Align with Vitiligo Disease Activity.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.032

Zhussipbek Mukhatayev, Artur Kovenskiy, Ziyou Ren, Stephanie M Rangel, Nurlubek Katkenov, Yerkhanat Khuanbai, Rohan Shivde, Moriel Daniel, Emilia R Dellacecca, Kettil Cedercreutz, Yekaterina Ostapchuk, Ayaulum Nurgozhina, Laura Chulenbayeva, Madiyar Nurgaziyev, Zharkyn Jarmukhanov, Marzhan Nurlankyzy, Kamilya Kozhdan, Symbat Seidulla, Zhanel Mukhanbetzhanova, Shynggyss Sergazy, Samat Kozhakhmetov, Yasmeen Ali, Karishma M Daftary, Stefan J Green, Roopal V Kundu, Almagul Kushugulova, I Caroline Le Poole

{"title":"Escherichia Abundance and Metabolism Align with Vitiligo Disease Activity.","authors":"Zhussipbek Mukhatayev, Artur Kovenskiy, Ziyou Ren, Stephanie M Rangel, Nurlubek Katkenov, Yerkhanat Khuanbai, Rohan Shivde, Moriel Daniel, Emilia R Dellacecca, Kettil Cedercreutz, Yekaterina Ostapchuk, Ayaulum Nurgozhina, Laura Chulenbayeva, Madiyar Nurgaziyev, Zharkyn Jarmukhanov, Marzhan Nurlankyzy, Kamilya Kozhdan, Symbat Seidulla, Zhanel Mukhanbetzhanova, Shynggyss Sergazy, Samat Kozhakhmetov, Yasmeen Ali, Karishma M Daftary, Stefan J Green, Roopal V Kundu, Almagul Kushugulova, I Caroline Le Poole","doi":"10.1016/j.jid.2025.01.032","DOIUrl":"10.1016/j.jid.2025.01.032","url":null,"abstract":"Vitiligo is a cutaneous autoimmune disorder characterized by progressive depigmentation due to melanocyte destruction by cytotoxic T cells. Genetic factors predispose patients to the disease and are supported by environmental factors that often initiate new disease episodes. We investigated whether disease outcomes were partially defined by pathogenic microbes that drive nutrient deficiency and inflammation. Our study presents the results of research on the diet and gut microbiome composition of patients with vitiligo and healthy controls from Kazakhstan and the United States. Dietary nutrient intake was assessed using the National Institutes of Health-generated Diet History Questionnaire. Patients with active vitiligo exhibit a limited intake of specific fatty acids, amino acids, fiber, and zinc. Disease activity was further characterized by the abundance of Odoribacter and Escherichia in the gut. Metabolic pathway analysis supported the role of the Escherichia genus in disease activity by limiting energy metabolism and amino acid biosynthetic pathways. Disease activity was also associated with elevated circulating proinflammatory cytokines. These findings suggest that nutritional limitations are not compensated by metabolites from the gut microbiome in active disease, potentially leaving room for inflammation and exacerbating vitiligo. The intricate relationship among diet, gut microbiome composition, and disease progression in vitiligo highlights potential avenues for targeted interventions to reduce autoimmune activity and improve patient outcomes.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473394","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}

引用次数: 0

Personalizing Biologic Therapy in Psoriasis: Development, Validation, and User Testing of a Precision-Dosing Dashboard.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.031

Charlotte M Thomas, David Baudry, Zehra Arkir, Bola Coker, Tejus Dasandi, Kingsley Powell, Monica Arenas-Hernandez, Jenny Leung, Krystal Rawstron, Chioma Nwaogu, Sarah Chapman, Richard Woolf, Andrew Pink, Jonathan Barker, Joseph F Standing, Catherine H Smith, Satveer K Mahil

{"title":"Personalizing Biologic Therapy in Psoriasis: Development, Validation, and User Testing of a Precision-Dosing Dashboard.","authors":"Charlotte M Thomas, David Baudry, Zehra Arkir, Bola Coker, Tejus Dasandi, Kingsley Powell, Monica Arenas-Hernandez, Jenny Leung, Krystal Rawstron, Chioma Nwaogu, Sarah Chapman, Richard Woolf, Andrew Pink, Jonathan Barker, Joseph F Standing, Catherine H Smith, Satveer K Mahil","doi":"10.1016/j.jid.2025.01.031","DOIUrl":"10.1016/j.jid.2025.01.031","url":null,"abstract":"An increasing number of individuals receiving psoriasis biologics achieve clear/nearly clear skin (disease control). Clinical trial data indicate that some maintain disease control with lower doses, especially those with higher serum drug concentrations. This indicates the potential of model-informed precision dosing, an advanced therapeutic drug-monitoring technique, to guide dose minimization. We developed, validated, and tested a precision-dosing dashboard. We applied a model-informed precision-dosing approach that leveraged Bayesian estimation to predict individual pharmacokinetic parameters for personalized dosing recommendations. A pharmacokinetic model of the exemplar biologic risankizumab derived from phases I-III psoriasis trial data (13,123 observations from 1899 patients) was externally validated using real-world data from the United Kingdom. The Bayesian model (posterior prediction: mean absolute error = 0.89 mg/l, mean percentage error = 19.55%, root mean square error = 1.24 mg/l, R2 = 0.86) had superior predictive power to the basic pharmacokinetic model (prior prediction). The model was incorporated into an interactive dashboard that enabled input of individual patient data (serum drug concentrations and model covariates). Healthcare professionals in the United Kingdom rated the dashboard as user friendly and acceptable. The mean time required to generate a dosing interval was 2 minutes. Our dashboard has the potential to incorporate other biologics and extend across disease contexts (nonresponse and other inflammatory diseases) for optimal real-world impact of precision dosing on health and cost outcomes.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473369","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}

引用次数: 0

Promising Exopolysaccharide as Complement to Conventional Therapy for Patients with Vitiligo.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.011

Meri K Tulic, Hanene Bzioueche

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PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.030

Michal Kidacki, Christina Cho, Francesc Lopez-Giraldez, Baozhu Huang, Jianwei He, Patricia Gaule, Lieping Chen, Matthew D Vesely

{"title":"PD-1H (VISTA) Expression in Cutaneous Squamous Cell Carcinoma Is Correlated with T-Cell Infiltration and Activation.","authors":"Michal Kidacki, Christina Cho, Francesc Lopez-Giraldez, Baozhu Huang, Jianwei He, Patricia Gaule, Lieping Chen, Matthew D Vesely","doi":"10.1016/j.jid.2025.01.030","DOIUrl":"10.1016/j.jid.2025.01.030","url":null,"abstract":"Cutaneous squamous cell carcinoma (cSCC) is one of the most common human cancers, with an estimated death rate approaching or exceeding that of melanoma. Immune inhibitory receptor antagonism through the blockade of PD-1 or its ligand, PD-L1, has revolutionized the treatment of cSCC; however, approximately half of patients still fail to respond. The inhibitory receptor PD-1H (also known as VISTA) controls T-cell and myeloid cell functions in preclinical cancer studies. Currently, cancer clinical trials using anti-VISTA-blocking antibodies are ongoing. We sought to determine the extent of VISTA expression in cSCCs and to correlate its expression with PD-L1 expression. Using multiplexed quantitative immunofluorescence of primary cSCC tissues (n = 76), we found that VISTA was expressed in 48% of cSCCs and that PD-L1 was expressed in 58% of cSCCs. We found that high VISTA expression, more than PD-L1 expression, correlated with greater T-cell infiltration and activation, as measured by the proliferation marker Ki-67 and the cytotoxic marker granzyme B. Furthermore, there was no significant correlation between VISTA and PD-L1 coexpression within the same cSCCs, suggesting that individual tumors have distinct immunosuppressive microenvironments. These findings provide a rationale for the targeting of VISTA in cSCC immunotherapy.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473368","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}

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Letter to the Editor in Response to Barbieri.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.028

Kaury Kucera, Christopher G Bunick, David Y Light

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Response to Wong et al.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2024.11.024

David C Whiteman, Catherine M Olsen, Nirmala Pandeya, Philip S Rosenberg

引用次数: 0

Genetic Risk Factors in Childhood Psoriasis.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.02.007

Christopher Willy Schwarz, Christoffer Blegvad, David Baudry, Isabella Tosi, Sang-Hyuck Lee, Raymond Chung, Esteban Tato-Barcia, Charles J Curtis, Catherine H Smith, Michael A Simpson, Anne-Marie Nybo Andersen, Jonathan N Barker, Paola Di Meglio, Lone Skov, Nick Dand

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Keratin Variants in Pyoderma Gangrenosum: Pathogenetic Insights from a Whole-Exome Sequencing-Based Bioinformatic Analysis.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.029

Chiara Moltrasio, Ronald Rodrigues Moura, Lucas Brandão, Paola Maura Tricarico, Muhammad Suleman, Carlo Alberto Maronese, Sergio Crovella, Angelo Valerio Marzano

{"title":"Keratin Variants in Pyoderma Gangrenosum: Pathogenetic Insights from a Whole-Exome Sequencing-Based Bioinformatic Analysis.","authors":"Chiara Moltrasio, Ronald Rodrigues Moura, Lucas Brandão, Paola Maura Tricarico, Muhammad Suleman, Carlo Alberto Maronese, Sergio Crovella, Angelo Valerio Marzano","doi":"10.1016/j.jid.2025.01.029","DOIUrl":"10.1016/j.jid.2025.01.029","url":null,"abstract":"Pyoderma gangrenosum (PG) is an inflammatory skin disorder that belongs to the group of neutrophilic dermatoses. Clinically, it is typified by cutaneous ulcers with distinctive erythematoviolaceous borders and may occur alone or in association with other inflammatory, autoinflammatory, or neoplastic conditions. Although its pathophysiology remains incompletely understood, mounting evidence points toward a predisposing genetic background and dysregulation of both the innate and adaptive immune responses, with follicular or epidermal structures as putative initial targets. To investigate the genetic factors associated with PG susceptibility and severity (arbitrarily defined as unilesional or multilesional), whole-exome sequencing was performed on 11 unrelated patients with PG. Eight strains carried at least 1 variant of the keratin-encoding gene, including keratin (K)18 gene K18, K20, K23, K32, and K33B. Strikingly, a recurrent variant (rs77999286) of the K18 gene was identified in 5 of 6 patients with multilesional PG and 1 of 5 of those with unilesional PG. AlphaFold modeling and mutation analysis revealed the destabilizing effect of the K18 rs77999286 variant on protein structure. Furthermore, immunohistochemistry revealed undetectable K18 staining in lesional skin compared with that in healthy control skin. Overall, these findings suggest that keratin variants may play a role in PG pathogenesis and indicate that the K18 rs77999286 variant is a potential genetic factor linked to multilesional disease.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473396","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}

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The Need for Transparency and Careful Messaging Regarding the Potential for Benzoyl Peroxide Products to Form Benzene.

The Journal of investigative dermatology Pub Date : 2025-02-19 DOI: 10.1016/j.jid.2025.01.027

John S Barbieri, Courtney B Rubin, James P Pham, Michelle Wong

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A Newly Identified Spliceosomal Protein AHED is Essential for Homeostasis of the Epidermis.

The Journal of investigative dermatology Pub Date : 2025-02-18 DOI: 10.1016/j.jid.2025.01.025

Mikiro Takaishi, Tatsushi Ishimoto, Sayo Kataoka, Ken-Ichi Yagyu, Keiko Morisawa, Sonoko Kinjo, Kazuho Ikeo, Shohei Noma, Chitose Takahashi, Yasushi Okazaki, Masahiro Tokunaga, Chikara Kokubu, Junji Takeda, Shigetoshi Sano

{"title":"A Newly Identified Spliceosomal Protein AHED is Essential for Homeostasis of the Epidermis.","authors":"Mikiro Takaishi, Tatsushi Ishimoto, Sayo Kataoka, Ken-Ichi Yagyu, Keiko Morisawa, Sonoko Kinjo, Kazuho Ikeo, Shohei Noma, Chitose Takahashi, Yasushi Okazaki, Masahiro Tokunaga, Chikara Kokubu, Junji Takeda, Shigetoshi Sano","doi":"10.1016/j.jid.2025.01.025","DOIUrl":"https://doi.org/10.1016/j.jid.2025.01.025","url":null,"abstract":"To identify genes that are essential for the functions of cells and organs, we established a homozygous mutant mouse embryonic stem cell bank from which we identified a gene, named Attenuated Hematopoietic Development (Ahed), that plays an essential role in hematopoiesis. Here, we characterize the role of AHED in the skin by analyzing mice with an epidermis-specific Ahed deficiency. Those mice have apoptotic cells in their epidermis from the perinatal stage. Thereafter, they develop skin barrier disruptions over time, which cause lethality soon after birth. Experiments using inducible Ahed deletion in vivo and in vitro revealed that an Ahed deficiency leads to keratinocyte apoptosis, impairs keratinocyte proliferation, and promotes dermatitis development. Since we found that AHED is a nuclear protein, we further revealed that AHED interacts with known spliceosomal proteins in HeLa cells. Moreover, altered splicing mRNA patterns were demonstrated in Ahed deficient keratinocytes. These results suggest that AHED plays a crucial role in the maintenance of epidermal integrity, and more importantly, it contributes to mRNA splicing that is essential for multiple cell lineages.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470408","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}

引用次数: 0