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The CD47 has been identified as a “do-not-eat” signal which is frequently overexpressed on tumor cells presenting a new therapeutic target as an innate checkpoint inhibitor. The mechanism by which anti-CD47 immunotherapy eliminate cutaneous lymphoma has not been explored. Here, we utilized depletion of NK cells and genetically IFN-γ deficient mice to elucidate the mechanism of anti-CD47 therapy in murine MBL2 model cutaneous T-cell lymphoma. We have demonstrated that CD47 is overexpressed on lymphoma cells when compared with the reactive T-cells in patients with tumor stage of mycosis fungodies (MF).
Rejection is the primary barrier to broader implementation of vascularized composite allografts (VCA) including face & limb transplants. We studied human face transplant rejection by gene expression profiling, histology and immunostaining. Unique aspects of face transplant rejection reflected the unique immunologic characteristics of skin, a barrier tissue populated by immune cells and rich in anti-inflammatory & immunomodulatory pathways. Grade 1 rejection, defined by Banff criteria, did not differ significantly from non-rejection; we suggest Grade 1 rejection is not a pathologic state and can be treated with watchful waiting.
Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation and dermal inflammation mediated by interleukin 17-producing T helper (Th17) cells. Previous studies have reported changes in Hedgehog (Hh) signaling in the lesional skin of psoriasis patients, but the functional consequence remains unknown. Here we show that downregulation of Hh signaling is associated with the development of imiquimod (IMQ)-induced psoriasis-like lesions in mice. Activation of Hh signaling by small-molecule Smoothened (Smo) agonist SAG increased the number of regulatory T cells and IL-10 expression, resulting in attenuation of IMQ-induced skin thickening and inflammation.
Our group has developed skin microsampling technology, microbiopsy, that enables the collection of tiny pieces of skin without causing pain nor local anaesthesia. The microbiopsyhas shown its potential as a tool for enabling molecular analysis. Photoageing causes chronic changes in skin that result in both aesthetic and medical issues. Our hypothesis is that a microsampling approach for studying photoageing would facilitate research in this field by improving safety, reducing risk, facilitating recruitment, enabling repeated sampling in cosmetically sensitive areas and permitting sampling in the same site over time.
Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and dermal tracts. We recently reported a high prevalence of anemia in HS patients (Soliman et al, 2018). This data led to the hypothesis that chronic inflammation in HS predominantly causes anemia of chronic disease (ACD) through upregulation of IL-6 and hepcidin, a key regulator of iron homeostasis. Hepcidin is widely accepted as a marker distinguishing ACD from iron deficiency anemia (IDA) in inflammatory conditions.
We have previously demonstrated that malignant T-cells in leukemic CTCL (L-CTCL) may simultaneously express mulitple immune checkpoint molecules, including PD-1, CTLA4 and TIGIT, possibly contributing to immune evasion and immune exhaustion and these may also have relevance to prognosis. The ability to block signaling of these molecules is likely to be beneficial to clinical outcome which is supported by preliminary data from trials using anti-PD-1 therapy for advanced CTCL. In this study we assessed the use of multiple immune checkpoint inhibitors on the proliferation and Th1 cytokine production of CD4 and CD8 T-cells of patients with L-CTCL.
Cutaneous T-cell lymphoma (CTCL) is a group of rare, heterogeneous lymphomas. Several therapies exist, but have limited patient efficacy without methods to predict responses. Recent characterization of the genomic landscape of CTCL revealed frequent alterations of important regulators of T-cell signaling, survival, and proliferation that may confer sensitivity or resistance to therapies. We therefore applied a novel hematolymphoid next-generation sequencing panel to inform treatments in a cohort of 57 patients with CTCL.
Dithranol (anthralin) has been one of the most potent topical treatments for psoriasis, yet its therapeutic mechanisms have remained largely unclear. In this study, biopsy samples (taken before, during and at end of dithranol treatment) from 15 psoriasis patients were analyzed using microarray gene expression analysis (Affymetrix Human Gene 2.0 Arrays) and differentially expressed genes (DEGs) were identified based on fold changes (>1.5) and t-test (P<0.05). To understand the molecular mechanisms underlying dithranol therapy, we compared our study with gene expression data from three published studies in psoriasis patients with agents targeting IL-17 (ixekizumab, GSE31652), IL-17 receptor (brodalumab, GSE53552) or TNF (etanercept, GSE11903).
Anecdotal evidence suggests dietary changes can reduce symptoms of hidradenitis suppurativa (HS). Evidence examining efficacy of dietary alteration is sparse, yet may be attractive to patients. The objective of this study is to investigate the prevalence and impact of dietary alteration among people with HS. A cross-section online survey was conducted from March to June 2018. Participants were recruited from ResearchMatch, Facebook, Reddit groups, and the Penn State Dermatology department. Participants were eligible if they could read in English, were 18 years of age or older, and had HS.
Antimalarials are the first-line therapy for cutaneous lupus erythematosus (CLE). While some of the patients that do not initially respond to hydroxychloroquine (HCQ) benefit from the addition of quinacrine (QC), there is a subset of patients that are refractory to both antimalarials. We investigated the immunologic characteristics of patients that respond to antimalarials versus nonresponders. CLE patients were classified as HCQ-responders, HCQ/QC-responders, or HCQ/QC-nonresponders. Immunohistochemistry and qRT-PCR for gene expression were used to characterize the inflammatory cell composition and cytokine expression in lesional skin biopsies from patients.
Hyperthermia has been clinically utilized as an optional therapy in the treatment of HPV-infected skin lesions by directly influencing virus activity and promoting host immune responses to eliminate HPV infections. However, thermotolerance induced by heme oxygenase-1 (HO-1), a stress-inducible cytoprotective protein, limits the efficacy of hyperthermic therapy, for which the exact mechanism remains unknown. In the present study, we found that heat treatment induced HO-1 expression, decreased copy number of HPV16 and altered the integration degree in HPV infected cell lines and tissues.
Interleukin (IL)-31 levels are elevated in skin and serum of patients with pruritic diseases. OSMRβ heterodimerizes with IL-31 receptor α or gp130 to form functional IL-31 and type II OSM receptors, respectively. KPL-716 targets OSMRβ and is a potential treatment for pruritic and fibrotic conditions. We optimized the dose of intradermal recombinant human IL-31, yielding a consistent, robust scratching response in cynomolgus monkeys and evaluated KPL-716 efficacy and PK/PD in this model. Scratching/grooming behavior was monitored with a Noldus Media Recorder pre- and post-IL-31 administration (3, 6, 12, or 24 μg/kg in 4 monkeys/group).
Recent research showed an increasing frequency of prescription drug overpayments, or “clawbacks,” where an insured patient’s copayment exceeds the insurer’s cost for the drug. To date, clawbacks have been quantified for the most commonly used oral drugs across all medical disciplines, however, clawbacks have not been assessed for topical drugs. The objective of this study was to investigate the frequency and cost of clawbacks for topical prescription drugs. The MarketScan database, a claims database of commercial private insurers, was searched for all claims of commonly prescribed topical drugs.
Dermatomyositis (DM) is an autoimmune disease affecting the skin, skeletal muscle, and/or lungs. While the pathogenesis remains poorly understood, it is thought to be driven largely by type 1 interferons (IFN-β) and involve CD4+ cells, mast cells, and dendritic cells. We aimed to explore expression of these cytokines and cells in relationship to the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) skin activity. We evaluated skin biopsies from 12 patients with moderate-severe cutaneous DM at baseline and after 12 weeks of treatment.
Premature neonates are highly susceptible to iatrogenic injury given an immature skin barrier. The removal of adhesives necessary for securing monitoring devices for severely premature neonates poses a risk for epidermal stripping, where up to 15% of a neonate’s total skin surface area can be traumatized daily. We introduce a pair of ultrathin, soft, skin-like electronic devices with a stress reducing microfluidic compartment whose coordinated, wireless operation reproduces the functionality of traditional monitoring systems but bypasses their intrinsic limitations.
Treatment with ruxolitinib cream (INCB18424; RUX) is associated with significant therapeutic benefit in mild to moderate atopic dermatitis patients. In comparison with vehicle and triamcinolone 0.1%, skin disease severity was improved to a greater degree following treatment with 1.5% RUX BID in a Phase 2b (NCT03011892) placebo-controlled clinical trial. This study investigated the effects of treatment with vehicle, triamcinolone 0.1%, 1.5% RUX QD, 1.5% RUX BID on inflammatory mediator expression in circulation.
Objective Topically applied Imiquimod is widely used for establishing animal model of psoriatic skin inflammation, while it is unclear whether long term treatment would also set up a model combined pathologcal changes in bone, liver and spleen. Our study aimed to observe whether the long term applied Imiquimod induce aberrant changes in bone, liver and spleen associated with psoriasis. Methords Three-month old Kunming mouse were randomly assigned to receive topical application of Imiquimod (5% cream, 50mg) or control cream on their shaved back, 7 days for 1-week group, then 5 days per week for 1-month and 3-month groups.
Despite revision of AJCC staging criteria, the identification and validation of credible prognostic biomarkers remains critical to identifying patients with high risk early stage melanomas, their subsequent counselling, stratification and follow up. Following the identification of AMBRA1 (a pro-autophagy regulatory protein) and Loricrin (a marker of terminal keratinocyte differentiation) as protein markers whose expression is lost in the epidermis overlying high risk primary AJCC stage I melanomas, the objective of the current study was to validate combined epidermal AMBRA1 and Loricrin (AMLo) as a prognostic biomarker for AJCC stage I melanoma.
Pemphigus is a group of life-threatening organ-specific autoimmune bullous disease, caused by autoantibodies directed against the desmosomal cadherins (desmoglein1 and/or desmoglein 3). Clinically, it was observed that the lesions are prone to affect the sebaceous-gland-rich areas and the recurrent lesions are at the same spot. We proposed that the local lesions might have the pathogenic memory in the disease development. In recent years, a newly identified subset of memory T cells, tissue-resident memory T (TRM) cellsare characterized gradually, which are non-recirculating memory T cells persisting long life in epithelial tissues, including skin, lung, and gastrointestinal tract, etc.