JID innovations : skin science from molecules to population health最新文献_第3页

Nanostring Transcriptomic Analysis Highlights IL-6 Family and TGF-β Pathways in the Pathogenesis of Prurigo Nodularis 纳米链转录组学分析揭示IL-6家族和TGF-β通路在结节性痒疹发病中的作用

JID innovations : skin science from molecules to population health

Pub Date : 2025-10-17 DOI: 10.1016/j.xjidi.2025.100422

Yagiz Matthew Akiska , Shrey Bhatt , Kavita Vats , Selina M. Yossef , Davies Gage , Shahin Shahsavari , Louis J. Born , Perya Bhagchandani , Deena Fayyad , Hannah Cornman , Thomas Pritchard , Jessica E. Teague , Rachael A. Clark , Madan M. Kwatra , Shawn G. Kwatra

Prurigo nodularis (PN) is a chronic, neuroimmune-driven skin disease characterized by intensely pruritic nodules and marked impairment in QOL. Although PN shares inflammatory features with atopic dermatitis and psoriasis, its underlying pathogenesis remains poorly defined. In this study, we performed NanoString-based transcriptomic profiling on lesional skin biopsies from patients with PN (n = 26), those with atopic dermatitis (n = 25), those with psoriasis (n = 15), and healthy controls (n = 12) using a custom neuroinflammation-focused panel. PN demonstrated a unique molecular signature involving neuroimmune activation (TMEM119, S100A10), extracellular matrix remodeling (matrix metalloproteinase 14 gene MMP14, COL6A3), and fibrotic signaling (TGFBR1, ITGB5), with IL-6 and MAPK12 as key inflammatory mediators. Compared with atopic dermatitis, PN displayed reduced T helper 2 signaling but greater neuroinflammatory and fibrotic activity. Relative to psoriasis, PN lacked T helper 17–driven hyperproliferation but showed macrophage and extracellular matrix activation. STRING network analysis also revealed IL-6 and TGF-β signaling as central hubs linking neuroinflammation and fibrosis. These findings establish PN as a distinct inflammatory skin disease at the intersection of neuroimmune dysregulation and tissue remodeling. Our results highlight key pathways that may guide precision therapies beyond current T helper 2–targeted treatments, supporting the development of IL-6, TGF-β, and Jak/signal transducer and activator of transcription–directed strategies in PN. This transcriptomic analysis establishes a framework to guide mechanistic and therapeutic investigations in PN.

结节性痒疹（PN）是一种慢性，神经免疫驱动的皮肤病，其特征是强烈的瘙痒结节和明显的生活质量损害。尽管PN与特应性皮炎和牛皮癣具有相同的炎症特征，但其潜在的发病机制仍不清楚。在这项研究中，我们使用定制的神经炎症聚焦小组，对PN患者（n = 26）、特应性皮炎患者（n = 25）、牛皮癣患者（n = 15）和健康对照组（n = 12）的病变皮肤活检进行了基于纳米串的转录组学分析。PN表现出独特的分子特征，包括神经免疫激活（TMEM119、S100A10）、细胞外基质重塑（基质金属蛋白酶14基因MMP14、COL6A3）和纤维化信号（TGFBR1、ITGB5），其中IL-6和MAPK12是关键的炎症介质。与特应性皮炎相比，PN显示T辅助2信号减少，但神经炎症和纤维化活性增强。相对于银屑病，PN缺乏T辅助17驱动的过度增生，但表现为巨噬细胞和细胞外基质活化。STRING网络分析也显示IL-6和TGF-β信号是连接神经炎症和纤维化的中枢枢纽。这些发现确定PN是一种独特的炎症性皮肤病，处于神经免疫失调和组织重塑的交叉点。我们的研究结果强调了可能指导精确治疗的关键途径，而不是目前的T辅助2靶向治疗，支持IL-6， TGF-β和Jak/信号转导和激活因子在PN中转录导向策略的发展。这种转录组学分析建立了一个框架来指导PN的机制和治疗研究。

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引用次数: 0

Clinician and Patient Perspectives in Oral Lichen Planus: Correlation and Drivers of Disease Severity and QOL 口腔扁平苔藓的临床和患者观点：疾病严重程度和生活质量的相关性和驱动因素

JID innovations : skin science from molecules to population health

Pub Date : 2025-10-17 DOI: 10.1016/j.xjidi.2025.100424

Emma L. Myers , Sarah G. McAlpine , Donna A. Culton

Oral lichen planus is a chronic, immune-mediated inflammatory condition that significantly impacts QOL. Clinician-reported measures, such as the Oral Disease Severity Score (ODSS), systematically evaluate clinical severity but may not adequately reflect patient experience. Patient-reported outcome measures, such as the Chronic Oral Mucosal Disease Questionnaire (COMDQ-26), provide QOL insights, although their relationship with clinical severity remains underexplored. This study aimed to assess alignment between clinician-assessed severity (measured by ODSS) and patient-reported QOL (measured by COMDQ-26) in oral lichen planus across sex and disease subtypes as well as to identify key drivers of these scores. A retrospective review of 78 patients with oral lichen planus was conducted with assessment of demographics, disease subtypes, ODSS, COMDQ-26, and pain scores. Erythematous and erosive/ulcerative subtypes had the highest severity and QOL impact scores, with no significant score differences between these subtypes. ODSS components (site, activity, pain) contributed equally to total severity, whereas the COMDQ-26 patient support domain most strongly drove QOL scores. Moderate ODSS–COMDQ-26 correlations indicated only partial alignment between clinician- and patient-reported measures. We conclude that integrating patient-reported outcome measures into clinical practice and trials may improve oral lichen planus care through more comprehensive, individualized, and subtype-focused strategies.

口腔扁平苔藓是一种慢性、免疫介导的炎症，显著影响生活质量。临床报告的措施，如口腔疾病严重程度评分（ODSS），系统地评估临床严重程度，但可能不能充分反映患者的经历。患者报告的结果测量，如慢性口腔黏膜疾病问卷（COMDQ-26），提供了生活质量的见解，尽管它们与临床严重程度的关系仍未得到充分探讨。本研究旨在评估临床评估的口腔扁平苔藓严重程度（由ODSS测量）和患者报告的生活质量（由COMDQ-26测量）在性别和疾病亚型之间的一致性，并确定这些评分的关键驱动因素。对78例口腔扁平苔藓患者进行回顾性分析，评估人口统计学、疾病亚型、ODSS、COMDQ-26和疼痛评分。红斑和糜烂/溃疡亚型的严重程度和生活质量影响评分最高，这些亚型之间没有显著的评分差异。ODSS成分（部位、活动、疼痛）对总严重程度的影响相同，而COMDQ-26患者支持域对生活质量评分的影响最大。适度的ODSS-COMDQ-26相关性表明，临床医生和患者报告的测量结果仅部分一致。我们的结论是，将患者报告的结果测量纳入临床实践和试验中，可以通过更全面、个性化和以亚型为重点的策略改善口腔扁平苔藓的护理。

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引用次数: 0

Lower Neighborhood Socioeconomic Status Is Associated with Moderate-Severe Hidradenitis Suppurativa: A Cross-Sectional Study 较低的社区社会经济地位与中重度化脓性汗腺炎相关：一项横断面研究

JID innovations : skin science from molecules to population health

Pub Date : 2025-10-17 DOI: 10.1016/j.xjidi.2025.100423

Maria Elena Sanchez-Anguiano , Krittin Supapannachart , Erin H. Amerson , Haley B. Naik , Stephen Shiboski , Mindy Hebert-Derouen , Jinoos Yazdany , Aileen Y. Chang

Neighborhood factors may impact hidradenitis suppurativa (HS) severity. Neighborhood environment influences obesity and smoking, which may affect HS severity. Longer time to diagnosis is correlated with worse HS severity at diagnosis, and dermatologists are not evenly distributed geographically. Two studies investigating the relationship between neighborhood socioeconomic status (SES) and HS severity reported contrasting results. We examine whether neighborhood SES is associated with HS severity at diagnosis within a health system using a census tract–level measure of neighborhood SES, adjusting for individual-level confounders and accounting for census tract clustering. In our cross-sectional study of 462 patients with a new HS diagnosis, patients residing in lower SES neighborhoods had greater odds of Hurley stage 2–3 disease in age- and sex-adjusted models (OR = 1.69, 95% confidence interval = 1.15–2.50, P = .008). Additional adjustment for race and ethnicity revealed a positive association that was not statistically significant (adjusted OR = 1.37, 95% confidence interval = 0.88–2.14, P = .16). Further adjustment for insurance type did not attenuate effect size. We observed evidence of a multiplicative interaction between neighborhood SES and race and ethnicity (P = .02). Residing in lower SES neighborhoods was associated with greater odds of moderate–severe HS at diagnosis. The relationship between neighborhood SES and race and ethnicity is complex, warranting further investigation.

社区因素可能影响化脓性汗腺炎（HS）的严重程度。社区环境影响肥胖和吸烟，这可能影响HS的严重程度。诊断时间较长与诊断时HS严重程度较差相关，并且皮肤科医生的地理分布不均匀。两项调查社区社会经济地位（SES）与HS严重程度之间关系的研究报告了截然相反的结果。我们使用人口普查区水平的社区SES测量方法，调整个人水平的混杂因素，并考虑人口普查区聚类，研究卫生系统中社区SES是否与诊断时HS严重程度相关。在我们对462例新诊断为HS的患者进行的横断面研究中，在年龄和性别调整模型中，居住在社会经济地位较低社区的患者患Hurley 2-3期疾病的几率更高（OR = 1.69, 95%置信区间= 1.15-2.50,P = 0.008）。对种族和民族进行额外调整后，发现两者呈正相关，但无统计学意义（调整后OR = 1.37, 95%可信区间= 0.88-2.14,P = 0.16）。进一步调整保险类型并没有减弱效应大小。我们观察到邻里社会经济地位与种族和民族之间存在乘法交互作用的证据（P = 0.02）。居住在社会经济地位较低的社区，在诊断时患中重度HS的几率更高。社区社会经济地位与种族和民族之间的关系是复杂的，需要进一步调查。

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引用次数: 0

Squaric Acid Dibutylester Promotes Innate Immune-Driven Hair Growth with CD206+ Macrophage Accumulation in the Dermis 方酸二丁酯通过真皮CD206+巨噬细胞积累促进先天免疫驱动的毛发生长

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-26 DOI: 10.1016/j.xjidi.2025.100420

Koichi Tomii , Madoka Ozawa , Yasuhiro Kanda , Daichi Kobayashi , Nan-Jun Li , Eiji Umemoto , Haruko Hayasaka , Michio Tomura , Arata Takeuchi , Riichiro Abe , Tomoya Katakai

Alopecia areata (AA) is an autoimmune skin disorder that causes hair loss. Squaric acid dibutylester (SADBE) is used for AA treatment as a topical immunotherapy that promotes hair growth by inducing allergic contact dermatitis in skin lesions. However, the mechanism of action remains unclear. C3H/HeJ mice spontaneously develop AA, and SADBE application induces hair growth at the lesion on day 28. In healthy young mice treated with SADBE, hair growth was observed after day 14. Fluorescent immunostaining of SADBE-treated skin tissues revealed a remarkable accumulation of macrophages in the dermis on day 3. These macrophages were divided into 3 subsets that formed a layered structure; in particular, CD206⁺F4/80⁺ cells were localized near the dermal papilla. Flow cytometric analysis also showed these 3 subsets in SADBE-treated skin on day 3. Macrophage depletion by intradermal clodronate injection inhibited SADBE-induced hair growth, suggesting macrophage dependency. A single SADBE application induced hair growth without sensitization, indicating that the acute inflammation mediated by innate immune cells was sufficient. Hair growth by repeated SADBE application in AA-affected mice closely correlated with the increase of CD206⁺ macrophages. These findings suggest that innate immune cells, particularly macrophages, play an important role in SADBE-induced hair growth, which would be potential targets in novel therapies for AA.

斑秃（AA）是一种导致脱发的自身免疫性皮肤疾病。方酸二丁酯（SADBE）是一种局部免疫疗法，用于AA治疗，通过在皮肤损伤处诱导过敏性接触性皮炎来促进头发生长。然而，其作用机制尚不清楚。C3H/HeJ小鼠自发发生AA，第28天应用SADBE诱导病灶处毛发生长。用SADBE治疗的健康幼鼠，14天后观察毛发生长。经sade处理的皮肤组织在第3天的荧光免疫染色显示真皮中巨噬细胞的显著积累。巨噬细胞分为3个亚群，形成层状结构；特别是CD206+F4/80+细胞位于真皮乳头附近。流式细胞术分析也显示，在第3天使用sade治疗的皮肤中有这3个亚群。皮内注射氯膦酸钠去巨噬细胞抑制sade诱导的毛发生长，提示巨噬细胞依赖性。单次应用SADBE诱导头发生长而不致敏，表明先天免疫细胞介导的急性炎症是足够的。反复应用SADBE对aa小鼠毛发生长的影响与CD206+巨噬细胞的增加密切相关。这些发现表明，先天免疫细胞，特别是巨噬细胞，在sadbe诱导的毛发生长中起着重要作用，这可能是AA新疗法的潜在靶点。

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引用次数: 0

Remote Skin and Blood Sampling for Translational Connective Tissue Disorder Research: A Proof-of-Concept Pilot Study 翻译结缔组织疾病研究的远程皮肤和血液采样：概念验证试点研究

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-26 DOI: 10.1016/j.xjidi.2025.100421

Dany Alkurdi , Saeed Shakiba , Isabel Okinedo , Faradia Kernizan , Ümmügülsüm Yildiz-Altay , Jane Vongvirath , Diana Reusch , Jillian Richmond

Remote, noninvasive biospecimen collection methods can address geographic and mobility-related barriers to participation in translational research for connective tissue disorders. We evaluated the feasibility of combining noninvasive skin tape stripping and Tasso capillary blood collection to molecularly profile lupus and morphea in remote settings using mailed kits. RNA extraction was optimized from 20 serial tape strips per site, with overnight shipping and scraping samples in buffer without sonication, yielding the highest concentration and quality. We enrolled 8 patients with lupus, 3 patients with morphea, and 8 healthy controls. Microarray analysis identified upregulation of CXCL9, CCR6, and PDGFRA in lupus and morphea skin. Proteomic analysis revealed elevated IFN-γ, TNFRSF4, and ANGPT2 in lupus serum, with lower IL-13 than in controls. Morphea samples showed increased expression of markers, including PDGFRA, P2RX1, and KALRN. Distinct gene expression signatures of CTGF, TNFRSF4, and MAFB in lupus skin and ALOX15, KALRN, and P2RX1 in morphea skin enabled differentiation between morphea and lupus. CXCL9 and IFN-γ biomarkers were confirmed in other publicly available datasets at both the protein and RNA levels. These findings provide proof of concept that remote RNA and protein profiling is feasible and reproducibly identifies canonical and, to our knowledge, previously unreported disease markers; however, the small number of patients and the lack of more complete characterization of the participants studied require that further studies are needed to establish the role of these findings in the pathogenesis of lupus and morphea. This approach enables broader inclusion of underserved patients and offers a scalable model for remote biomarker studies in dermatologic and autoimmune research.

远程、非侵入性生物标本收集方法可以解决地理和流动性相关的障碍，以参与结缔组织疾病的转化研究。我们评估了将无创皮肤胶带剥离和Tasso毛细管血液采集相结合的可行性，以使用邮寄试剂盒在偏远地区对狼疮和吗啡进行分子分析。每个位点有20个串行磁带条优化RNA提取，隔夜运输和在缓冲液中刮取样品，不需要超声波，可以获得最高的浓度和质量。我们招募了8名狼疮患者，3名吗啡患者和8名健康对照。微阵列分析发现，狼疮和鼹鼠皮肤中CXCL9、CCR6和PDGFRA表达上调。蛋白质组学分析显示狼疮患者血清中IFN-γ、TNFRSF4和ANGPT2升高，IL-13低于对照组。Morphea样品显示标记物表达增加，包括PDGFRA、P2RX1和KALRN。狼疮皮肤中的CTGF、TNFRSF4和MAFB以及狼疮皮肤中的ALOX15、KALRN和P2RX1基因表达特征不同，这使得狼疮和狼疮之间存在分化。CXCL9和IFN-γ生物标志物在其他公开可用的蛋白质和RNA水平数据集中得到证实。这些发现证明了远程RNA和蛋白质分析是可行的，并且可重复地识别规范的，据我们所知，以前未报道的疾病标志物；然而，由于患者数量少，且研究对象缺乏更完整的特征，因此需要进一步的研究来确定这些发现在狼疮和狼疮发病机制中的作用。这种方法能够更广泛地纳入服务不足的患者，并为皮肤病学和自身免疫研究中的远程生物标志物研究提供了可扩展的模型。

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引用次数: 0

SOX2 Is a Potential Diagnostic Biomarker and Anticancer Target in Cutaneous Squamous Cell Carcinoma in Dystrophic Epidermolysis Bullosa: A Case Series Study SOX2是营养不良大疱性表皮松解症皮肤鳞状细胞癌的潜在诊断生物标志物和抗癌靶点：一项病例系列研究

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-22 DOI: 10.1016/j.xjidi.2025.100417

Clara Harrs , Marieke Bolling , Peter van den Akker , Bart Koopman , Barbara Horváth , Gilles Diercks , Léon van Kempen

A serious complication in epidermolysis bullosa (EB), particularly in recessive dystrophic EB, is the development of aggressive cutaneous squamous cell carcinoma with a high risk for metastasis and poor survival outcomes. The current standard of care is insufficient, and there is a critical need for safe and effective management options for this life-threatening complication in EB. Moreover, the pathophysiologic processes behind the aggressiveness of EB-associated cutaneous squamous cell carcinoma (EB-cSCC) remain elusive. Especially little is known about genetic drivers specific for EB-cSCC, and information about the molecular profile of these highly malignant tumors could lead to novel insights about the underlying pathogenesis. In addition, EB-associated pseudoepitheliomatous hyperplasia (EB-PEH) is difficult to distinguish from EB-cSCC histologically and could be a premalignant precursor of EB-cSCC. Therefore, the aim of this study was to conduct gene expression profiling to detect potentially diagnostic biomarkers and anticancer targets in EB-cSCC and explore the potential role of EB-PEH in the tumorigenesis of EB-cSCC. We performed mRNA expression analysis and immunohistochemistry on formalin-fixed, paraffin-embedded tissue samples of EB-cSCCs (n = 8), non–EB-cSCCs (n = 10), and EB-PEHs (n = 7). The results revealed upregulation of SOX2 mRNA expression in EB-cSCCs compared with that in non–EB-cSCCs, albeit in this study, the sample size was small, and cases and controls were not age matched, which may limit interpretation of our findings. In addition, immunohistochemical staining showed increased SOX2 protein expression in EB-cSCCs compared with that in non–EB-cSCCs. SOX2 protein expression was also observed in EB-PEH, with 1 case showing a transition from SOX2-negative to SOX2-positive cells, indicating the possible initiation of an EB-cSCC in situ. Further validation of the study results, including mechanistic studies, is needed before the utility of SOX2 as a biomarker can be assessed. However, these findings propose that SOX2 may play a role in the development of aggressive EB-cSCC and could serve as a potential biomarker of progression from benign EB-PEH to EB-cSCC.

大疱性表皮松解症（EB）的一个严重并发症，尤其是隐性营养不良EB，是发展为侵袭性皮肤鳞状细胞癌，转移风险高，生存预后差。目前的护理标准是不够的，对于这种危及生命的EB并发症，迫切需要安全有效的管理选择。此外，eb相关性皮肤鳞状细胞癌（EB-cSCC）侵袭性背后的病理生理过程仍然难以捉摸。特别是对EB-cSCC的遗传驱动知之甚少，而关于这些高度恶性肿瘤的分子特征的信息可能会导致对潜在发病机制的新见解。此外，eb相关的假上皮瘤性增生（EB-PEH）在组织学上难以与EB-cSCC区分，可能是EB-cSCC的癌前前兆。因此，本研究的目的是通过基因表达谱检测EB-cSCC中潜在的诊断性生物标志物和抗癌靶点，并探讨EB-PEH在EB-cSCC肿瘤发生中的潜在作用。我们对EB-cSCCs （n = 8）、非EB-cSCCs （n = 10）和EB-PEHs （n = 7）的福尔马林固定、石蜡包埋组织样本进行了mRNA表达分析和免疫组化。结果显示，与非EB-cSCCs相比，EB-cSCCs中的SOX2 mRNA表达上调，尽管在本研究中，样本量很小，病例和对照组的年龄不匹配，这可能限制了我们研究结果的解释。此外，免疫组化染色显示，与非EB-cSCCs相比，EB-cSCCs中SOX2蛋白表达增加。在EB-PEH中也观察到SOX2蛋白表达，其中1例显示从SOX2阴性细胞向SOX2阳性细胞转变，表明可能原位启动EB-cSCC。在评估SOX2作为生物标志物的效用之前，需要进一步验证研究结果，包括机制研究。然而，这些研究结果表明，SOX2可能在侵袭性EB-cSCC的发展中发挥作用，并可能作为良性EB-PEH向EB-cSCC进展的潜在生物标志物。

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引用次数: 0

High Prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients with Hidradenitis Suppurativa: A Guide to Easily Assess the Clinical Risk of Comorbid Liver Disease 化脓性汗腺炎患者中代谢功能障碍相关脂肪变性肝病的高发率：一个容易评估合并症肝病临床风险的指南

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-22 DOI: 10.1016/j.xjidi.2025.100419

Verena G. Frings , Maxine Gläsel , Monika Rau , Andreas Geier , Janik Fleißner , Dagmar Presser , Matthias Goebeler , Andreas Kerstan

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with considerable comorbidity. The link between HS and metabolic dysfunction–associated steatotic liver disease (MASLD) is of particular interest owing to shared inflammatory pathways. This study applies the new MASLD nomenclature in a HS cohort. Our study aims to investigate the prevalence of MASLD in HS using transient elastography and to develop a clinical algorithm for assessing the MASLD risk. A cross-sectional study was conducted involving 94 patients with HS. Noninvasive methods were employed to diagnose MASLD. The clinical diagnosis was based on altered transient elastography–controlled attenuation parameter as surrogate for liver steatosis and the presence of cardiometabolic risk factors after excluding secondary causes of steatosis. Statistical analyses included logistic regression models to identify predictors of MASLD risk. The study found a prevalence of MASLD as high as 75% measured by high-accuracy transient elastography among patients with HS. Multivariable logistic regression analysis showed a strong within-cohort association between HS and MASLD. The newly developed clinical algorithm integrating transient elastography and the Fatty Liver Index effectively stratified MASLD risk. Our findings underscore the importance of routine MASLD screening in HS. The proposed clinical algorithm offers a straightforward approach for assessing MASLD risk in HS.

化脓性汗腺炎（HS）是一种慢性炎症性皮肤病，有相当多的合并症。HS与代谢功能障碍相关的脂肪变性肝病（MASLD）之间的联系由于共同的炎症途径而引起特别关注。本研究在HS队列中应用新的MASLD命名法。我们的研究目的是利用瞬态弹性成像来调查HS中MASLD的患病率，并开发一种评估MASLD风险的临床算法。对94例HS患者进行了横断面研究。采用无创方法诊断MASLD。临床诊断是基于改变的瞬时弹性成像控制衰减参数作为肝脏脂肪变性的替代指标，并在排除脂肪变性的继发原因后存在心脏代谢危险因素。统计分析包括逻辑回归模型，以确定MASLD风险的预测因子。研究发现，通过高精度瞬态弹性成像测量，HS患者的MASLD患病率高达75%。多变量logistic回归分析显示HS和MASLD之间有很强的队列内相关性。新开发的结合瞬态弹性成像和脂肪肝指数的临床算法有效地对MASLD风险进行分层。我们的研究结果强调了HS常规MASLD筛查的重要性。所提出的临床算法为评估HS的MASLD风险提供了一种直接的方法。

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引用次数: 0

ZNF750 Loss of Function Drives Spontaneous Psoriasiform Skin Inflammation ZNF750功能丧失驱动自发性牛皮癣样皮肤炎症

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-17 DOI: 10.1016/j.xjidi.2025.100416

Hilla Levi , Topaz Alfer , Roi Gazit , Idan Cohen

Epidermal keratinocytes are not only crucial for maintaining skin barrier physical functions but also play various roles in the initiation, progression, and maintenance phases of skin inflammation. ZNF750 is an epithelial-specific transcription factor expressed in differentiating keratinocytes, whose activity is required for keratinocyte terminal differentiation. In humans, ZNF750 sequence variant causes psoriasis-like skin disease. In this study, using a genetic mouse model to study the role played by ZNF750 in epidermal homeostasis, we reveal that ZNF750 activity is essential for preventing skin inflammation. We show that a loss of ZNF750 activity results in the rapid development of psoriasiform skin lesions. Molecular dissection further demonstrated an impaired balance between epidermal cell proliferation and differentiation, induction of proinflammatory factors by Znf750-deficient keratinocytes, and a massive immune cell infiltration. Altogether, our study highlights the importance of keratinocytes in inflammatory skin disease pathogenesis, demonstrating ZNF750 loss-of-function sufficiency in driving severe psoriasiform skin inflammation, which resembles the diseased human condition in patients with pathogenic ZNF750 sequence variants.

表皮角质形成细胞不仅对维持皮肤屏障物理功能至关重要，而且在皮肤炎症的发生、发展和维持阶段发挥着各种作用。ZNF750是一种在角质形成细胞分化中表达的上皮特异性转录因子，其活性是角质形成细胞终末分化所必需的。在人类中，ZNF750序列变异导致牛皮癣样皮肤病。在这项研究中，我们使用一个遗传小鼠模型来研究ZNF750在表皮稳态中所起的作用，我们发现ZNF750活性对于预防皮肤炎症是必不可少的。我们发现ZNF750活性的丧失会导致银屑病样皮肤病变的快速发展。分子解剖进一步证实了表皮细胞增殖和分化之间的平衡受损，znf750缺陷角质形成细胞诱导促炎因子，以及大量免疫细胞浸润。总之，我们的研究强调了角质形成细胞在炎症性皮肤病发病机制中的重要性，证明了ZNF750功能丧失足以驱动严重的牛皮癣状皮肤炎症，这与具有致病性ZNF750序列变异的患者的患病状况相似。

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引用次数: 0

Peptide Epitopes of NC16A BP180 in the Diagnostics of Bullous Pemphigoid NC16A BP180肽表位在大疱性类天疱疮诊断中的意义

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-12 DOI: 10.1016/j.xjidi.2025.100415

Simon D. Lytton , Christine Wagger , Damian Meyersburg , Birgit Mussnig , Roland Lang , Roberto Maglie , Florian Anzengruber , Emiliano Antiga , Russell P. Hall , Johann W. Bauer

Bullous pemphigoid is a severe autoimmune blistering skin disorder causing significant morbidity and mortality among the elderly. Improved diagnostic strategies rely on the identification of autoantigen epitopes recognized by pathogenic autoantibodies. Continuous (linear) peptide epitopes, unlike conformational epitopes in recombinant proteins, offer advantages such as chemical stability, reproducibility, and lower production costs, making them attractive for diagnostic assay development. To identify relevant linear epitopes, a microarray of overlapping peptides spanning the NC16A domain of BP180 and the C-terminus of BP230 autoantigens was screened with sera of 13 patients with bullous pemphigoid and 2 control sera. A 25-mer peptide of NC16A, termed Pep7-NC16A, was evaluated by ELISA in 2 independent patient cohorts (n = 35 and 26 bullous pemphigoid cases, n = 48 and 53 controls). Pep7-NC16A ELISA showed sensitivity of 71% and 62% and specificity of 92% and 98%, with area under the curve values of 0.92 and 0.754 (P < .001). Reactivity strongly correlated with commercial BP180 NC16A ELISA (r = 0.72, P < .0001). In this study, we demonstrate the diagnostic potential of synthetic peptide in bullous pemphigoid. The identified epitope could also serve as a potential biomarker for BP180-associated conditions or future peptide-based immunotherapies.

大疱性类天疱疮是一种严重的自身免疫性皮肤病，在老年人中引起显著的发病率和死亡率。改进的诊断策略依赖于病原性自身抗体识别的自身抗原表位的鉴定。与重组蛋白中的构象表位不同，连续（线性）肽表位具有化学稳定性、可重复性和较低的生产成本等优点，因此对诊断分析开发具有吸引力。为了确定相关的线性表位，我们从13例大疱性类天疱疮患者和2例对照血清中筛选了跨越BP180的NC16A结构域和BP230自身抗原c端重叠肽的微阵列。在2个独立的患者队列（35例和26例大疱性类天疱疮患者，48例和53例对照组）中，用ELISA法评估了NC16A的一种25-mer肽，称为Pep7-NC16A。Pep7-NC16A ELISA检测的灵敏度分别为71%和62%，特异性分别为92%和98%，曲线下面积分别为0.92和0.754 （P < .001）。反应性与商用BP180 NC16A ELISA有很强的相关性（r = 0.72, P < 0.0001）。在这项研究中，我们证明了合成肽在大疱性类天疱疮中的诊断潜力。所鉴定的表位也可以作为bp180相关疾病或未来基于肽的免疫疗法的潜在生物标志物。

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引用次数: 0

Increased Risk of Postoperative Complications in Patients with Hypertension Undergoing Mohs Micrographic Surgery 接受莫氏显微摄影手术的高血压患者术后并发症的风险增加

JID innovations : skin science from molecules to population health

Pub Date : 2025-09-08 DOI: 10.1016/j.xjidi.2025.100414

Alexandra Elder , Henry Y. Yang , Megan O’Donnell-Cappelli , Jenna L. Mandel , Molly Wallace , Lauren Banner , Ramsay Hafer , Thomas Z. Rohan , Neda Nikbakht

Hypertension has been previously associated with higher intraoperative bleeding risk in patients undergoing Mohs micrographic surgery. However, the risks of common postoperative Mohs micrographic surgery complications have not been substantiated by large studies. Our study aimed to assess the risks of common Mohs micrographic surgery complications for patients with hypertension utilizing the TriNetX database, a global health records database encompassing over 105 million patients’ data, from January 2009 to January 2024. After 1:1 propensity score matching for age, sex, race, diabetes, nicotine dependence, obesity, and anticoagulant use, the final analysis included 80,739 patients in each cohort of patients with hypertension and matched controls. We found that within a 60-day postoperative period, patients with hypertension had a significantly higher risk of bleeding both intraoperatively (OR = 2.19, 95% confidence interval = 1.39–3.46) and postoperatively (OR = 2.11, 95% confidence interval = 1.44–3.09). In addition, patients with hypertension faced a significantly higher risk of various postoperative infections such as gangrene (OR = 2.17, 95% confidence interval = 1.24–3.79) and impaired wound healing (OR = 1.25, 95% confidence interval = 1.06–1.48). Results did not vary significantly by stage of hypertension. Essential hypertension is associated with significantly increased intraoperative and postoperative hemorrhage, infections, and wound disruptions; thus, it may be beneficial to assess and risk stratify patients with hypertension before performing Mohs micrographic surgery.

高血压与莫氏显微摄影手术患者术中出血风险增高有关。然而，常见的术后莫氏显微摄影手术并发症的风险尚未得到大型研究的证实。我们的研究旨在利用TriNetX数据库（包含2009年1月至2024年1月超过1.05亿患者数据的全球健康记录数据库）评估高血压患者常见莫氏显微摄影手术并发症的风险。在对年龄、性别、种族、糖尿病、尼古丁依赖、肥胖和抗凝剂使用进行1:1的倾向评分匹配后，最终的分析包括每组高血压患者和匹配对照组的80,739例患者。我们发现，在术后60天内，高血压患者术中（OR = 2.19, 95%可信区间= 1.39-3.46）和术后（OR = 2.11, 95%可信区间= 1.44-3.09）出血的风险均显著增高。此外，高血压患者术后发生坏疽（OR = 2.17, 95%可信区间= 1.24-3.79）、创面愈合受损（OR = 1.25, 95%可信区间= 1.06-1.48）等各种感染的风险明显较高。不同阶段高血压的结果无显著差异。原发性高血压与术中和术后出血、感染和伤口破裂显著增加有关；因此，在进行莫氏显微摄影手术前对高血压患者进行评估和风险分层可能是有益的。

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引用次数: 0