{"title":"NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype","authors":"Marietta Schindler , Paula Schuster-Winkelmann , Veronika Weß , Sophia Czell , Franziska Rueff , Andreas Wollenberg , Matthias Siebeck , Roswitha Gropp","doi":"10.1016/j.xjidi.2024.100268","DOIUrl":"10.1016/j.xjidi.2024.100268","url":null,"abstract":"<div><p>NSG (NOD/Scid IL2Rγ<sup>null</sup>) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000146/pdfft?md5=00fd321e7bee9d649d4f7311c571778b&pid=1-s2.0-S2667026724000146-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139875284","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 Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning","authors":"Yayoi Kamata , Rui Kato , Mitsutoshi Tominaga , Sumika Toyama , Eriko Komiya , Jun Utsumi , Takahide Kaneko , Yasushi Suga , Kenji Takamori","doi":"10.1016/j.xjidi.2024.100271","DOIUrl":"10.1016/j.xjidi.2024.100271","url":null,"abstract":"<div><p>Hand–foot skin reaction is the most common adverse event of multikinase inhibitors, such as sorafenib. Although hand–foot skin reaction is not life threatening, severe cases impair quality of life because of pain and reduced activities of daily living. However, the pathological mechanisms of hand–foot skin reaction have not yet been elucidated in detail, and there is currently no effective treatment. We aimed to identify keratinocyte cytoprotectants against sorafenib toxicity. The screening of cytoprotectants against sorafenib toxicity was performed using cultured normal human epidermal keratinocytes or a reconstructed human epidermis model and off-patent approved drugs in the Prestwick Chemical library. Among 1273 drugs in the chemical library, 8 dose-dependently increased cell viability by >200% in the presence of sorafenib. In the presence of sorafenib, the number of proliferating cell nuclear antigen–positive cells was significantly higher in clofazimine-, cyclosporin A–, and itraconazole-treated reconstructed human epidermis models than in sorafenib-treated models, and candidate drugs suppressed sorafenib-induced apoptosis in normal human epidermal keratinocytes. In addition, clofazimine, itraconazole, and pyrvinium pamoate significantly recovered the phosphorylation of extracellular signal–regulated kinase 1/2 in the presence of sorafenib. Collectively, hit drugs promoted cell viability and normalized keratinocyte proliferation in the presence of sorafenib. These candidate drugs have potential as treatments for multikinase inhibitor–induced hand–foot skin reaction.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000183/pdfft?md5=6ac09b2f5c88dad96300d97f7d0fd131&pid=1-s2.0-S2667026724000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140470031","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}
Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka
{"title":"In Silico Elucidation of Key Drivers of Staphyloccocus aureus–Staphyloccocus epidermidis–Induced Skin Damage in Atopic Dermatitis Lesions","authors":"Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka","doi":"10.1016/j.xjidi.2024.100269","DOIUrl":"10.1016/j.xjidi.2024.100269","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em> (SA) colonizes and can damage skin in atopic dermatitis lesions, despite being commonly found with <em>Staphylococcus epidermidis</em> (SE), a commensal that can inhibit SA’s virulence and kill SA. In this study, we developed an <em>in silico</em> model, termed a virtual skin site, describing the dynamic interplay between SA, SE, and the skin barrier in atopic dermatitis lesions to investigate the mechanisms driving skin damage by SA and SE. We generated 10<sup>6</sup> virtual skin sites by varying model parameters to represent different skin physiologies and bacterial properties. <em>In silico</em> analysis revealed that virtual skin sites with no skin damage in the model were characterized by parameters representing stronger SA and SE growth attenuation than those with skin damage. This inspired an <em>in silico</em> treatment strategy combining SA-killing with an enhanced SA–SE growth attenuation, which was found through simulations to recover many more damaged virtual skin sites to a non-damaged state, compared with SA-killing alone. This study demonstrates that <em>in silico</em> modelling can help elucidate the key factors driving skin damage caused by SA–SE colonization in atopic dermatitis lesions and help propose strategies to control it, which we envision will contribute to the design of promising treatments for clinical studies.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400016X/pdfft?md5=178aabaf5651f027521d8120342ea113&pid=1-s2.0-S266702672400016X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467524","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":"Inflammatory Memory in Chronic Skin Disease","authors":"Joseph A. Daccache , Shruti Naik","doi":"10.1016/j.xjidi.2024.100277","DOIUrl":"10.1016/j.xjidi.2024.100277","url":null,"abstract":"<div><p>Inflammation is a hallmark of remitting-relapsing dermatological diseases. Although a large emphasis has been placed on adaptive immune cells as mediators of relapse, evidence in epithelial and innate immune biology suggests that disease memory is widespread. In this study, we bring to the fore the concept of inflammatory memory or nonspecific training of long-lived cells in the skin, highlighting the epigenetic and other mechanisms that propagate memory at the cellular level. We place these findings in the context of psoriasis, a prototypic flaring disease known to have localized memory, and underscore the importance of targeting memory to limit disease flares.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872479","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}
Sarah A. Mullen , Emma L. Myers , Rebecca L. Brenner , Kim T. Nguyen , Tara A. Harper , Darby Welsh , Storm Keffer , Jenna Mueller , Melodi Javid Whitley
{"title":"Systematic Review of Intralesional Therapies for Cutaneous Warts","authors":"Sarah A. Mullen , Emma L. Myers , Rebecca L. Brenner , Kim T. Nguyen , Tara A. Harper , Darby Welsh , Storm Keffer , Jenna Mueller , Melodi Javid Whitley","doi":"10.1016/j.xjidi.2024.100264","DOIUrl":"10.1016/j.xjidi.2024.100264","url":null,"abstract":"<div><p>Intralesional therapies are used for recalcitrant warts, but no Food and Drug Administration–approved treatment exists nor is there consensus regarding the most efficacious therapy. Therefore, this systematic review aims to summarize efficacy and adverse events reported in 62 randomized controlled trials (RCTs) of intralesional therapies for cutaneous warts. The most studied intralesional therapies included measles, mumps, rubella (MMR) vaccine (n = 24 studies), purified protein derivative (PPD) (n = 19 studies), vitamin D3 (n = 15 studies), and Candida antigen (n = 14 studies). Most studies included adult and pediatric patients or adults alone, with only 4 studies on pediatric patients alone. MMR vaccine was the most studied treatment (n = 853 patients). MMR had a complete response rate of 27–90%. The next most common treatment, PPD, had a complete response rate of 45–87%. Other treatments included Candida antigen and vitamin D3, with complete response rates of 25–84% and 40–96%, respectively. The most frequent side effects were injection-site reactions and flu-like symptoms. This systematic review represents a useful summary of intralesional therapy RCTs for clinician reference. This study also highlights the lack of large multi-institutional RCTs, despite many patients being treated for this widespread problem.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000109/pdfft?md5=cf21b5dcafa5a1711fe7695ee5532160&pid=1-s2.0-S2667026724000109-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139632661","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}
Lindsey G. Siegfried , Sophie M. Bilik , Jamie L. Burgess , Paola Catanuto , Ivan Jozic , Irena Pastar , Rivka C. Stone , Marjana Tomic-Canic
{"title":"An Optimized and Advanced Algorithm for the Quantification of Immunohistochemical Biomarkers in Keratinocytes","authors":"Lindsey G. Siegfried , Sophie M. Bilik , Jamie L. Burgess , Paola Catanuto , Ivan Jozic , Irena Pastar , Rivka C. Stone , Marjana Tomic-Canic","doi":"10.1016/j.xjidi.2024.100270","DOIUrl":"10.1016/j.xjidi.2024.100270","url":null,"abstract":"<div><p>Advancements in pathology have given rise to software applications intended to minimize human error and improve efficacy of image analysis. Still, the subjectivity of image quantification performed manually and the limitations of the most ubiquitous tissue stain analysis software requiring parameters tuned by the observer, reveal the need for a highly accurate, automated nuclear quantification software specific to immunohistochemistry, with improved precision and efficiency compared with the methods currently in use. We present a method for the quantification of immunohistochemical biomarkers in keratinocyte nuclei proposed to overcome these limitations, contributing sensitive shape-focused segmentation, accurate nuclear detection, and automated device-independent color assessment, without observer-dependent analysis parameters.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000171/pdfft?md5=d3e1293c9de3ee42e7a6f4a0308b4765&pid=1-s2.0-S2667026724000171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965668","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}
Florentine L. de Boer , Henk F. van der Molen , Jen-Hung Wang , Ellen Raun , Jorge Pereda , Edwin En-Te Hwu , Ivone Jakasa , Sandrine Dubrac , Thomas Rustemeyer , Sanja Kezic
{"title":"Skin Barrier– and Immune Response–Related Biomarkers of Solar UVR Exposure Comparing Indoor and Outdoor Workers","authors":"Florentine L. de Boer , Henk F. van der Molen , Jen-Hung Wang , Ellen Raun , Jorge Pereda , Edwin En-Te Hwu , Ivone Jakasa , Sandrine Dubrac , Thomas Rustemeyer , Sanja Kezic","doi":"10.1016/j.xjidi.2024.100280","DOIUrl":"10.1016/j.xjidi.2024.100280","url":null,"abstract":"<div><p>Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers. Using a linear mixed model adjusting for age and skin phototype, we compared biomarkers between both skin sites in indoor and outdoor workers. We measured markers of the immune response and skin barrier, including cytokines, GFs, 15-hydroxyeicosatetraenoic acid, cis- and <em>trans</em>-urocanic acid, and corneocyte topography, indicated by circular nano objects. Differences between the 2 skin sites were found for cis-urocanic acid, total urocanic acid, IL-1α, IL-1RA, IL-1RA/IL-1α, IL-18, 15-hydroxyeicosatetraenoic acid, CCL4, and circular nano objects. The levels of cis-urocanic acid and CCL4 also differed between indoor and outdoor workers. These findings underscore changes in both immune response and skin barrier induced by UVR. They indicate the potential utility of stratum corneum biomarkers in detecting both chronic UVR exposure in occupational setting and aiding in the development of preventive measures.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000274/pdfft?md5=d28d1a7220a0b9d9874db0551d5797ff&pid=1-s2.0-S2667026724000274-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794024","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":"Molecular Analysis of Murine KitK641E Melanoma Progression","authors":"Emily Everdell , Zhenyu Ji , Ching-Ni Njauw , Hensin Tsao","doi":"10.1016/j.xjidi.2024.100266","DOIUrl":"10.1016/j.xjidi.2024.100266","url":null,"abstract":"<div><p>Acral and mucosal melanomas are often driven by sequence variants in the KIT receptor tyrosine kinase, with nearly 40% harboring alterations in the <em>KIT</em> locus. Despite advances in the knowledge of <em>KIT</em>-mutated melanomas, little is known about the molecular reprogramming that occurs during KIT-mediated melanoma progression owing to the rarity of acral and mucosal melanomas and the lack of comprehensive biological tools and models. To this end, we used a murine model that allows us to ascertain the molecular underpinnings of the stages of cancer progression—transformation, tumorigenesis, immune engagement, and tumor escalation. We found dramatic increases in biosynthetic demands associated with the transformation stage, including DNA and RNA metabolism, leading to replication stress. Tumorigenesis was closely linked to neuronal and axonal development, likely necessary for invasion into the host. Immune engagement highlighted early immune excitation and rejection pathways, possibly triggered by abrupt neoantigen exposure. Finally, tumor escalation pathways proved consistent with immune evasion, with immune-related pathways becoming significantly downregulated. To our knowledge, it is previously unreported that these critical milestones needed for KIT-driven melanoma tumor formation have been studied at the molecular level using isogenically matched and phenotypically defined cells.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000122/pdfft?md5=5b2a6d12bc9524b3679788530b36ea31&pid=1-s2.0-S2667026724000122-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140518492","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}
Olivia G. Cohen , Matthew Taylor , Cassandra Mohr , Kevin T. Nead , Candice L. Hinkston , Sharon H. Giordano , Sinead M. Langan , David J. Margolis , Mackenzie R. Wehner
{"title":"Antihypertensive Medications and Risk of Melanoma and Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis","authors":"Olivia G. Cohen , Matthew Taylor , Cassandra Mohr , Kevin T. Nead , Candice L. Hinkston , Sharon H. Giordano , Sinead M. Langan , David J. Margolis , Mackenzie R. Wehner","doi":"10.1016/j.xjidi.2024.100272","DOIUrl":"10.1016/j.xjidi.2024.100272","url":null,"abstract":"<div><p>Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose–response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11–1.22), diuretics (RR = 1.06, 95% CI = 1.03–1.10), and thiazides (RR = 1.10, 95% CI = 1.04–1.16); for squamous cell carcinoma with calcium channel blockers (RR = 1.08, 95% CI = 1.01–1.14), diuretics (RR = 1.29, 95% CI = 1.17–1.43), and thiazides (RR = 1.36, 95% CI = 1.15–1.61); and for melanoma in angiotensin-converting enzyme inhibitors (RR = 1.09, 95% CI = 1.03–1.14), calcium channel blockers (RR = 1.08, 95% CI = 1.03–1.12), and thiazides (RR = 1.09, 95% CI = 1.02–1.17). The quality of evidence was low or very low. We observed evidence for dose–response for thiazides with basal cell carcinoma; angiotensin-converting enzyme inhibitors, diuretics, and thiazides with squamous cell carcinoma; and angiotensin-converting enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100272"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000195/pdfft?md5=0a6957143e51e056ecf1465c49643308&pid=1-s2.0-S2667026724000195-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271747","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}
Aditi Gadre , Taylor Dyson , Jaroslaw Jedrych , Grant Anhalt , Angel S. Byrd , Crystal Aguh
{"title":"Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation","authors":"Aditi Gadre , Taylor Dyson , Jaroslaw Jedrych , Grant Anhalt , Angel S. Byrd , Crystal Aguh","doi":"10.1016/j.xjidi.2024.100263","DOIUrl":"10.1016/j.xjidi.2024.100263","url":null,"abstract":"<div><p>Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1–mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (<em>IGHG3</em>, <em>P</em> = .034; <em>IGHG4</em>, <em>P</em> = .01; <em>IGG1</em>, <em>P</em> = .026) and markers of fibrosis (<em>ITGA1</em>, <em>P</em> = .016; <em>SFRP2</em>, <em>P</em> = .045; <em>TPM2</em>, <em>P</em> = .029; <em>SLMAP</em>, <em>P</em> = .016) and downregulation of metabolic proteins (<em>ALOX15B</em>, <em>P</em> = .003; <em>FADS2</em>, <em>P</em> = .006; <em>ELOVL5</em>, <em>P</em> = .007; <em>FA2H</em>, <em>P</em> = .017; <em>FAR2</em>, <em>P</em> = .011; <em>SC5D</em>, <em>P</em> < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100263"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000092/pdfft?md5=242f9089c5d1e9424470c2e861e5aafe&pid=1-s2.0-S2667026724000092-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139632789","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}