Inhibition of RNase 7 by RNase inhibitor promotes inflammation and Staphylococcus aureus growth: Implications for atopic dermatitis.

Background: The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7-RI interactions on AD.

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis.

Background: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab - a monoclonal antibody that neutralizes IL-13 - reduces inflammation and clinical disease activity, less is known about its effects on barrier function.

Objectives: To characterize the effects of tralokinumab treatment on skin barrier function.

Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

Background: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD.

Objectives: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD.

Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin.

Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD.

Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry.

Methods: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine.

miRNA expression profiles of the perilesional skin of atopic dermatitis and psoriasis patients are highly similar.

Atopic dermatitis (AD) and psoriasis vulgaris (PV) are chronic inflammatory skin diseases with heterogeneous molecular backgrounds. MicroRNAs (miRNAs) contribute to either development or regulation of many immune system related diseases. Only few miRNA profiling studies are available for AD and no comparisons between AD and PV skin miRNA profiles have been performed recently.

Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota.

Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts.

Quantitative Proteomics Identifies Reduced NRF2 Activity and Mitochondrial Dysfunction in Atopic Dermatitis.

Atopic dermatitis is the most common inflammatory skin disease and is characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in atopic dermatitis pathogenesis, but the alterations in the proteome that occur in the full epidermis have not been defined. Using a pressure-cycling technology and data-independent acquisition approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and nonlesional patient skin.

Blood transcriptome profiling identifies 2 candidate endotypes of atopic dermatitis.

Background: Few studies have analyzed the blood transcriptome in atopic dermatitis (AD).

Objective: We explored blood transcriptomic features of moderate to severe AD.

Methods: Blood messenger RNA sequencing on 60 adults from the TREATgermany registry including 49 patients before and after dupilumab treatment, as well as from an independent cohort of 31 patients and 43 controls was performed.

Comparison of Epidermal Barrier Integrity in Adults with Classic Atopic Dermatitis, Atopic Prurigo and Non-Atopic Prurigo Nodularis.

A deficient epidermal barrier is a key feature of atopic dermatitis (AD) and comprises altered lipid and protein content and composition of the stratum corneum resulting in disturbed water balance. Clinically, eczematous lesions on dry skin and pruritus develop. Pruritic nodules occur in prurigo nodularis (PN), another chronic skin disease, which can be associated with atopy.

The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases.

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome.

Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis.

Background: Altered quantities, activity, and composition of natural killer (NK) cells in blood as well as expression changes of genes involved in NK-cell function in skin lesions of patients with atopic dermatitis (AD) were recently reported.

Objectives: We sought to comprehensively analyze cutaneous NK-cell transcriptomic signatures in AD, and to examine changes under treatment.

Methods: We analyzed NK-cell signatures in skin transcriptome data from 57 patients with moderate to severe AD and 31 healthy controls.

Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome.

Background: Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers.

Effectiveness of secondary prevention in metalworkers with work-related skin diseases and comparison with participants of a tertiary prevention program: A prospective cohort study.

Background: In Germany, a multistep approach has been established to prevent work-related skin diseases (WRSDs).

Objectives: To evaluate the effect of a secondary individual prevention program (SIP) in metalworkers with WRSD and to compare their characteristics with those of participants of a tertiary individual prevention program (TIP).

Patients And Methods: In a prospective cohort study, metalworkers with WRSD of the hands participating either in the SIP (n = 114) or in the TIP (n = 83) were recruited.

NADPH oxidase inhibition rescues keratinocytes from elevated oxidative stress in a 2D atopic dermatitis and psoriasis model.

Emerging evidence suggests oxidative stress plays a role in the pathophysiology of both atopic dermatitis (AD) and psoriasis (PSO). We established in vitro models of AD and PSO skin, and characterized these models in regard to their oxidative stress state. Both AD and PSO model keratinocytes exhibited elevated reactive oxygen species (ROS) levels and accumulated more DNA damage than control cells after oxidative stress induced by 250 µmol/L H O .

Atopic dermatitis displays stable and dynamic skin transcriptome signatures.

Background: Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as "improvement" under therapy. These observations were mainly made in trials and based on microarray data.

Objectives: Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry.

Health education decreases incidence of hand eczema in metal work apprentices: Results of a controlled intervention study.

Background: Metal work apprentices (MWAs) frequently develop work-related hand eczema (HE).

Objectives: To evaluate the effect of health education on incidence of work-related HE in MWAs and to assess confounding factors.

Materials/methods: In a prospective controlled intervention study, 131 MWAs received educational training on prevention of HE, whereas 172 MWAs and 118 office work apprentices served as controls.

Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently.

The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function.

Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses.

Background: Although multiple studies have assessed molecular changes in chronic atopic dermatitis (AD) lesions, little is known about the transition from acute to chronic disease stages, and the factors and mechanisms that shape chronic inflammatory activity.

Objectives: We sought to assess the global transcriptome changes that characterize the progression from acute to chronic stages of AD.

Methods: We analyzed transcriptome changes in paired nonlesional skin, acute and chronic AD lesions from 11 patients and 38 healthy controls by RNA-sequencing, and conducted in vivo and histological assays to evaluate findings.