Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA389673 | ENA |
REPOSITORIES: ENA
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Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4R? that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials 18 Patients with AD treated with dupilumab or placebo. 28 biopsies in lesional (LS) Skin (16 pre-treatment and 12 post-treatment). 12 biopsies in non-lesional (NL) Skin (7 pre-treatment and 5 post treatment)
2014-12-04 | E-GEOD-59294 | biostudies-arrayexpress
Project description:A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD).
2018-10-06 | GSE120899 | GEO
Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4Rα that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials
2014-12-04 | GSE59294 | GEO
Project description:Background: Chronic hand eczema (CHE) is a debilitating skin condition characterized by pain, itch, and chronic inflammation, with a complex multifactorial origin. Its diverse presentations, including overlapping traits of atopic dermatitis, contact dermatitis, and psoriasis, make diagnosis and treatment particularly challenging. The underlying immune mechanisms of CHE still need to be investigated.Methods: Here we conducted a comprehensive molecular profiling of CHE patients, enrolled without prior selection on etiology and morphology, and performed a phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial comparing dupilumab to placebo over 16 weeks.Results: We demonstrated that CHE patients may benefit from IL4Rα-blockade, regardless of etiological factors or clinical presentation. Skin transcriptomic and serum profiles of CHE patients closely resemble those seen in both atopic dermatitis and psoriasis, with dysregulated genes affecting keratinocyte differentiation, leucocyte-mediated immunity, cytokine signaling, and mixed type 1, 2, and 3 immunity. The clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of all CHE patients while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis.Conclusion: These findings confirmed the involvement of not only type 2 but also type 1 and type 3 immunity across all CHE patients, and demonstrate that IL-4Rα blockade may offer effective therapeutic perspectives for this highly burdensome condition, independent of an atopic dermatitis background.
2026-02-26 | PXD059218 | Pride
Project description:Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis
| PRJNA590500 | ENA
Project description:Chronic hand eczema (CHE) is a painful, itchy and inflammatory skin disease of multifactorial origin. CHE can be categorized based on etiology and/or clinical presentation, including intertwined atopic-contact eczema-psoriasis traits, making it challenging to diagnose and treat. While being the most frequent work-related dermatosis, the underlying immune mechanisms remain unclear. Here we performed a randomized controlled study comparing dupilumab and placebo and demonstrated that CHE is a type 2 immunity driven disease, regardless of etiological factors or clinical presentation. We conducted a comprehensive molecular profiling of CHE patients of all etiologies and morphologies to identify potential common features and evaluated the consequences of blocking IL-4Rα during 16 weeks. This phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. We found that CHE patients share complex transcriptomic signatures with those of atopic dermatitis and psoriasis patients, with dysregulated genes involved in skin barrier, leukocyte migration, cytotoxicity, type 1, 2 and 3 immunity. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of CHE patients, while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis. These findings demonstrate that IL-4Rα signaling is a critical regulator of CHE pathological features, independent of atopic dermatitis background or environmental triggers, and propose reclassifying CHE as a type 2 immune disorder, with dupilumab or IL-4/13 targeted therapy as the mainstay treatment for moderate to severe disease.
2026-01-24 | GSE279422 | GEO
Project description:We conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD unresponsive to conventional topical or systemic treatment. Fezakinumab (ILV-094; anti IL-22 monoclonal antibody) monotherapy was administered for 12 weeks (primary endpoint), and clinical responses were followed until week 20. AD transcriptome significantly improved at week 12 in fezakinumab vs. placebo (p<1E-18).
2018-09-17 | GSE99802 | GEO
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description:This phase 1b, single-center, double-blind study evaluated safety, efficacy, and effect on molecular profiles of a topical Janus kinase/spleen tyrosine kinase (JAK/Syk) inhibitor, cerdulatinib gel 0.37%, in ten adults with mild-to-moderate atopic dermatitis (AD).
2020-11-12 | GSE141570 | GEO
Project description:Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action (MOA) of crisaborole and its effects on lesional measures of disease severity are not yet well-defined. This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the MOA of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (N = 40) with mild-to-moderate AD.
2019-06-29 | GSE133477 | GEO