Subcutaneous adipose tissue: Implications in dermatological diseases and beyond.

Subcutaneous adipose tissue (SAT) is the deepest component of the three-layered cutaneous integument. While mesenteric adipose tissue-based immune processes have gained recognition in the context of the metabolic syndrome, SAT has been traditionally considered primarily for energy storage, with less attention to its immune functions. SAT harbors a reservoir of immune and stromal cells that significantly impact metabolic and immunologic processes not only in the skin, but even on a systemic level.

Consensus Recommendations for the Management of Atopic Dermatitis in the United Arab Emirates.

Atopic dermatitis often begins in infancy and follows a chronic course of exacerbations and remissions. The etiology is complex and involves numerous factors that contribute to skin barrier defect and inflammation. In the Middle East, the burden of atopic dermatitis is understudied.

Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics.

Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) assess the effects of therapeutics for chronic wounds ex vivo.

IgE Depletion with Ligelizumab Does Not Significantly Improve Clinical Symptoms in Patients with Moderate-to-Severe Atopic Dermatitis.

Background: The value, if any, of anti-IgE approaches in the treatment of atopic dermatitis has not been fully clarified. Studies using the anti-IgE omalizumab have yielded conflicting results.

Objective: Antibodies with an IgE-suppressive capacity stronger than omalizumab might be more efficacious.

Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials.

Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from 5 phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.

Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells.

People living with HIV (PLWH) are at increased risk for developing skin and mucosal malignancies despite systemic reconstitution of CD4 T cells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-related immunodeficiency in HIV is unclear. We found that skin CD4 tissue-resident memory T (Trm) cells were depleted after HIV infection and replenished only upon early ART initiation.

Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma.

Background: In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20-30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood.

Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis.

Background: Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin's innate immune system.

Objective: To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions.

Methods: Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals.

Single-cell RNA sequencing profiling in a patient with discordant primary cutaneous B-cell and T-cell lymphoma reveals micromilieu-driven immune skewing.

Background: Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood.

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Die äußere Begrenzung des Körpers von Säugetieren, die Haut, besteht aus drei Schichten, Epidermis, Dermis und subkutanem weissem Fettgewebe (subcutaneous white adipose tissue, SWAT). Während die Epidermis und Dermis hinsichtlich ihrer Funktion als «Immunbarriere» eingehend charakterisiert sind, ist über das SWAT nur wenig bekannt. SWAT des Menschen setzt sich aus Läppchen zusammen, die vor allem aus Adipozyten bestehen und durch vaskularisierte Bindegewebssepten unterteilt und voneinander getrennt werden.

Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease.

The skin contains a population of tissue-resident memory T cells (T) that is thought to contribute to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of T has been obtained from murine studies, little is known about the biology of human cutaneous T Here, we showed that host-derived CD69 αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting T in the skin, whereas tissue retention molecules and stem cell markers were displayed by T The transcription factor RUNX3 and the surface molecule galectin-3 were preferentially expressed by host T cells at the RNA and protein levels, suggesting two new markers for human skin T Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived T, suggesting a contribution of these cells to the pathogenesis of GVHD.

Subcutaneous white adipose tissue: The deepest layer of the cutaneous immune barrier.

Mammalian skin, the outer covering of the body, is composed of three layers, i.e. the epidermis, the dermis and the subcutaneous white adipose tissue (SWAT).

[European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology].

Background And Objectives: Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future.

The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.

Background: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization.

Objectives: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability.

Prevalence of Skin-specific Autoantibodies in HIV-infected Patients and Uninfected Controls.

Various autoantibodies are detected more frequently in HIV-infected individuals than in HIV-negative controls; however, limited data exist regarding autoimmune blistering skin diseases. Using enzyme-linked immunoassay (ELISA) and indirect immunofluore-scence, no difference in the frequency and magnitude of autoantibodies against BP180, BP230, desmoglein 1 and 3 was found between 594 HIV-infected patients and 248 uninfected controls in this cross-sectional study (16.0% vs.

Specific Inhibition of the Classical Complement Pathway Prevents C3 Deposition along the Dermal-Epidermal Junction in Bullous Pemphigoid.

Deposition of autoantibodies (α-BP180 and BP230) and complement along the dermal-epidermal-junction is a hallmark of bullous pemphigoid and was shown to be important for pathogenesis. Given the adverse effects of standard treatment (glucocorticoids, immunosuppressants), there is an unmet need for safe and effective therapies. In this phase 1 trial, we evaluated the safety and activity of BIVV009 (sutimlimab, previously TNT009), a targeted C1s inhibitor, in 10 subjects with active or past bullous pemphigoid (NCT02502903).