The development and initial evaluation of conversation cards for optimizing consultations for patients with atopic dermatitis.

Purpose: Patients with atopic dermatitis (AD) require both skills and support to effectively manage life with the disease. Here, we developed an agenda-setting tool for consultations with patients with AD to establish a collaborative agenda that enhances patient involvement and prioritizes on self-management support.Materials and methods: Using the design thinking process, we included 64 end-users (patients and healthcare professionals (HCPs)) across the different phases of design thinking. We identified seven overall categories that patients find important to discuss during consultations, which informed the development of a tool for co-creating a consultation agenda (conversation cards, CCs).Results: Through iterative user testing of the CCs, patients perceived the cards as both inspiring and an invitation from HCPs to openly discuss their needs during consultations. Healthcare professionals have found the CCs easy to use, despite the disruption to the typical consultation process.Conclusion: In summary, the CCs provide a first-of-its-kind agenda-setting tool for patients with AD. They offer a simple and practical method to establishing a shared agenda that focuses on the patients' needs and are applicable within real-world clinical settings.

Mapping the Periostin splice isoforms in atopic dermatitis and an in vitro asthma model - A multi-platform analysis using mass spectrometry and RT-qPCR.

Periostin is a matricellular protein known to be alternatively spliced to produce ten isoforms with a molecular weight of 78-91 kDa. Within the extracellular matrix, periostin attaches to cell surfaces to induce signaling via integrin-binding and actively participates in fibrillogenesis, orchestrating the arrangement of collagen in the extracellular environment. In atopic diseases such as atopic dermatitis (AD) and asthma, periostin is known to participate in driving the disease-causing type 2 inflammation. The periostin isoforms expressed in these diseases and the implication of the alternative splicing events are unknown. Here, we present two universal assays to map the expression of periostin isoforms at the mRNA (RT-qPCR) and protein (PRM-based mass spectrometry) levels. We use these assays to study the splicing profile of periostin in AD lesions as well as in in vitro models of AD and asthma. In these conditions, periostin displayed overexpression with isoforms 3 and 5 standing out as highly overexpressed. Notably, isoforms 9 and 10 exhibited a divergent pattern relative to the remaining isoforms. Isoforms 9 and 10 are often overlooked in periostin research and this paper presents the first evidence of their expression at the protein level. This underlines the necessity to include isoforms 9 and 10 in future research addressing periostin splice isoforms. The assays presented in this paper hold the potential to improve our insight into the splicing profile of periostin in tissues and diseases of interest. The application of these assays to AD lesions and in vitro models demonstrated their potential for identifying isoforms of particular significance, warranting a further in-depth investigation.

Parents of children with atopic diseases - experiences with care and the interaction with healthcare professionals over time.

OBJECTIVE: To explore how the parents of children with atopic dermatitis and allergic diseases such as food allergy, allergic rhinoconjunctivitis, and asthma experience interactions with the Danish healthcare system over time. DESIGN AND METHODS: A qualitative design with individual in-depth interviews. The analysis was inspired by Systematic Text Condensation. SUBJECTS: Eleven parents of children with atopic dermatitis and allergic diseases who received treatment at hospitals in the Capital Region of Denmark. The families had experiences of cross-sectoral patient care. RESULTS: Despite having the same diseases, the children's care pathways were very different. Mapping demonstrated the intricacy of care pathways for this group of children. We identified three aspects that impacted interaction with healthcare: responsibility, tasks, and roles. The families experienced care when the distribution of tasks and responsibilities associated with treatment and system navigation were consistent with both their expectations and their actual experiences. At the same time, families frequently experienced limited collaboration between healthcare professionals resulting in perceived fragmented care and an extended role for parents as care coordinators. Families felt cared for when healthcare professionals knew both their biomedical and biographical circumstances, and adjusted the level of support and care in accordance with the families' particular needs, expectations, and evolving competences. CONCLUSION: We suggest that a possible pathway to improve care may be through a partnership approach as part of family-centered care, with general practitioners having a key role in helping to articulate the individual needs and expectations of each family.

The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.

Referral Pathways for Children with Atopic Diseases in Denmark.

Atopic diseases such as atopic dermatitis, food allergy, allergic rhinoconjunctivitis, and/or asthma are common. In Denmark, however, there are multiple referral pathways for these diseases in the healthcare system and they are poorly understood. To describe how children with atopic diseases navigate their way through the Danish healthcare system, a questionnaire was distributed to children aged ≤ 17 years, who were being treated for atopic diseases between August 2020 and June 2021, either by a practising specialist or a hospital department, in the Capital Region of Denmark. A total of 279 children completed the questionnaire and most were referred to a specialist or to a hospital by their general practitioner. No "common track" to hospital existed for patients with ≥ 3 atopic diseases. These patients were more often referred to a hospital compared with children with 2 atopic diseases or fewer (odds ratio [OR] 3.79; 95% CI 2.07-7.24). The primary determinants for hospital treatment were food allergy (OR 4.69; 95% CI 2.07-10.61) and asthma (OR 2.58; 95% CI 1.18-5.63). In conclusion, children with multiple atopic diseases were more likely to be referred to hospital departments than to practising specialists, mainly due to food allergies.

Clinical Characteristics Associated With Response to Biologics in the Treatment of Psoriasis: A Meta-analysis.

Importance: Clinical characteristics associated with treatment response to biologics in patients with psoriasis have never been systematically investigated. Objective: To evaluate the association between patient clinical characteristics and the effectiveness of biologics in treating psoriasis. Data Sources: PubMed, Embase, and Web of Science were searched from their inception through April 2022. Studies in English language that reported response to biologic treatment at approved doses in patients with psoriasis in relation to their clinical characteristics were included. In addition, eligible studies were identified through a search of the reference lists of the included studies. Study Selection: We only included studies that reported treatment outcomes as Psoriasis Area and Severity Index (PASI) 75 or PASI 90 after 12, 26, and/or 52 weeks of treatment. Both observational studies and randomized clinical trials (RCTs) were considered. Two independent authors conducted the screening process, and 107 studies were assessed for eligibility. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Relevant data were extracted independently by 2 authors. Data were pooled using random-effects models. RCTs and observational studies were pooled in separate analyses. Data were analyzed from June 1, 2023, to August 1, 2023. Main Outcomes and Measures: The primary outcome was PASI 90 at 26 weeks (6 months). Before data collection began, an investigation of the association between the main (and secondary) outcomes and several clinical characteristics was planned. Results: Overall, 40 studies with a total of 21 438 patients were included. Older age (odds ratio [OR], 0.99; 95% CI, 0.98-1.00), previous exposure to biologics (OR, 0.44; 95% CI, 0.29-0.67), higher body mass index (BMI) (OR, 0.96; 95% CI, 0.94-0.99), previous smoking (OR, 0.81; 95% CI, 0.67-0.98), and current smoking (OR, 0.78; 95% CI, 0.66-0.91) were negatively associated with achieving PASI 90 at 6 months in observational studies. In RCTs, only BMI of 30 or higher was negatively associated with treatment response (PASI 90 at 3 months: OR, 0.57; 95% CI, 0.48-0.66). Conclusions and Relevance: This meta-analysis found that patients with psoriasis who smoke or have a history of smoking, as well as those with previous exposure to biologics, older age, or higher BMI, exhibited poorer response to biologics in observational studies. However, it remains unclear whether these clinical characteristics influence treatment response differently for the different biologics available for psoriasis.

Psoriasis and mental health in adolescents: A cross-sectional study within the Danish National Birth Cohort.

BACKGROUND: Psoriasis is a chronic skin disease associated with lower quality of life and higher risk of anxiety and depression in adults. We investigate whether adolescents with psoriasis also experience poorer mental health than their peers. METHODS: In this cross-sectional study, we included questionnaire data on psoriasis and mental health from the 18-year follow-up of the Danish National Birth Cohort. We estimated odds ratios (OR) and 95 % confidence intervals (CI) using a logistic regression with inverse probability weighting to account for potential selection bias, adjusted for potential confounders identified a priori. We estimated associations between self-reported psoriasis and multiple aspects of mental health (self-rated health, life satisfaction, mental well-being, loneliness, overall and internalizing behavioral difficulties, depressive symptoms, and anxiety symptoms). In sensitivity analyses, we examined doctor-diagnosed psoriasis and psoriasis with and without joint pain. RESULTS: Of the 44,838 included in this study, 1147 (2.6 %) reported psoriasis. Adolescents with psoriasis had a higher risk of nearly all outcomes, including depressive symptoms (OR 1.38; 1.19-1.58) and panic/agoraphobia among both males (OR 1.72; 1.33-2.19) and females (OR 1.60; 1.33-1.92). Associations attenuated when restricted to doctor-diagnosed psoriasis. Associations with poor mental health were mainly observed for adolescents with psoriasis also reporting joint pain. LIMITATIONS: We could not establish temporality and lacked data on joint pain in referents. CONCLUSION: Psoriasis is associated with poor mental health in adolescents. This appears to be driven by adolescents with psoriasis also reporting joint pain and is less evident in those with a doctor-confirmed diagnosis.

Psychological burden, anxiety, depression and quality of life in patients with hand eczema: A systematic review and meta-analysis.

BACKGROUND: Living with hand eczema (HE) has been associated with impaired quality of life (QoL), having anxiety and depression but the magnitude of association is not clear. OBJECTIVES: The aim of this systematic review and meta-analysis was to determine the psychological burden in terms of anxiety, depression and quality of life in patients with HE. METHODS: Several databases were systematically searched. Weighted means with standard deviation (SD) were calculated for disease severity, QoL, depression and/or anxiety scores among patients with HE. For studies presenting QoL, depression and/or anxiety scores in patients with HE and in controls the weighted means were compared with an unpaired t-test. In studies reporting Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI), the correlation between HECSI and DLQI was estimated using Spearman's rank correlation (rs). RESULTS: In total, 81 studies encompassing 17,835 patients with HE and 31,541 controls were included. The weighted mean DLQI was 10.66 (SD 8.93) corresponding to a moderate-to-large effect on QoL and a strong correlation (rs: 0.76, 95% CI:0.56-0.87) between DLQI and HECSI was observed. The mean EQ-5D-VAS was significantly lower in patients with HE compared with controls (68.03 (SD 10.52) vs. 80.63 (SD 1.17), p < 0.00001). Patients with HE had higher mean HADS (Hospital Anxiety and Depression Scale) anxiety score (7.4 vs. 5.8, p = 0.0008) than controls but not higher HADS depression score (6.5 vs. 5.7, p = 0.32). Only one study assessed risk of anxiety, depression and suicidal ideation showing an increased odds of all diseases among patients with HE compared with controls. CONCLUSION: Hand eczema has a moderate-to-severe impact on quality of life with a strong correlation between disease severity and impact on quality of life. Patients with hand eczema have an impact on QoL comparable to other chronic diseases when measured with generic QoL scoring systems.

Alcohol consumption and risk of psoriasis: Results from observational and genetic analyses in more than 100,000 individuals from the Danish general population.

Background: Psoriasis is associated with high alcohol consumption, but the causality of this relationship is unclear. Objective: We aimed to use a Mendelian randomization approach to investigate the causal effects of alcohol on incident psoriasis. Methods: We included 102,655 adults from the prospective Copenhagen studies. All participants filled out a questionnaire on alcohol consumption, were physically examined, and had blood drawn for biochemical and genetic analyses. We created a genetic instrument based on the number of fast-metabolizing alleles in alcohol dehydrogenase 1B and alcohol dehydrogenase 1C, known to be associated with alcohol consumption, to test whether alcohol consumption was causally associated with psoriasis. Results: Observationally, we found an increased risk of incident psoriasis among individuals with high alcohol consumption compared to those with low alcohol consumption with a hazard ratio of 1.30 (95% confidence interval 1.05-1.60) in the fully adjusted model. Using genetic data to predict alcohol consumption to avoid confounding and reverse causation, we found no association between number of fast-metabolizing alleles and risk of psoriasis. Limitations: Alcohol consumption was self-reported and psoriasis was defined using the International Classification of Diseases 10th revision and 8th revision codes. Conclusion: Alcohol consumption is observationally but not causally associated with incident psoriasis.

Adherence to general national dietary guidelines and risk of psoriasis: results from a general population study of 105,332 individuals.

BACKGROUND: It is unknown if an unhealthy diet can affect the risk of developing psoriasis. OBJECTIVES: We hypothesised that individuals with an unhealthy diet have increased risk of prevalent and incident psoriasis. METHODS: We included 105,332 adults from the Copenhagen General Population Study, who were invited between 2003 and 2015. Response-rate was 43%. An unhealthy versus healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into low, intermediate, and high adherence to general national dietary guidelines based on information from a food frequency questionnaire. Identification of psoriasis was made using ICD codes. RESULTS: Of the 105,332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to non-adherence to general national dietary guidelines in a stepwise manner with an age and sex adjusted odds ratio of 1.70 (95% confidence interval 1.26-2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable adjusted model. Prospective analyses adjusted for age and sex showed a weak association between non-adherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). CONCLUSIONS: Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis.

Self-management Support for Patients with Atopic Dermatitis: A Qualitative Interview Study.

Patients with a chronic skin disease, eg, atopic dermatitis, need self-management skills to increase their quality of life. We explored patients' needs for self-management support from healthcare professionals and how these needs can be met in a dermatology setting. Interpretive description methodology was chosen for iterative data collection and analysis of qualitative interviews with patients with atopic dermatitis. Two mutually dependent themes were found to be supportive of patients' self-management. Personal and disease-related recognition was fundamental to successful support. However, guidance for agenda-setting from healthcare professionals was also needed on the wide range of topics that could be covered in the consultation based on individual needs. Patients need self-management support in addition to what can be found with family, friends, or peers. It is crucial that the support is delivered with an appreciative approach by healthcare professionals with profound knowledge of atopic dermatitis. Equally important is guidance towards agenda-setting, a way to co-construct the consultation with a clear focus on the specific patient's needs.

Stratum Corneum Lipids in Non-Lesional Atopic and Healthy Skin following Moisturizer Application: A Randomized Clinical Experiment.

INTRODUCTION: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). METHODS: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. RESULTS: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. CONCLUSION: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective.

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Atopic dermatitis (AD), and psoriasis are long-term skin conditions that can significantly affect people's lives, especially when symptoms are severe. Approximately 10% of adults and 20% of children are affected by AD, while psoriasis affects around 5% of people in the UK. Both conditions are associated with debilitating physical symptoms (such as itch) and have been linked to depression and anxiety. Biomarkers are naturally occurring chemicals in the human body and have potential to enhance the longer-term management of AD and psoriasis. Currently, there are no routinely used biomarkers that can identify people who experience or will go on to develop severe AD and psoriasis. For this reason, research is under way to understand which biomarkers are linked to severity. In this study, a multidisciplinary team of skin researchers from across Europe, along with patient groups, discussed the complexities of studying severity-related biomarkers. We identified a number of severity measurement approaches and there were recommendations for future biomarker research, including (i) considering multiple measures as no single measure can encompass all aspects of severity, (ii) exploring severity measures recorded by both healthcare professionals and patients, as each may capture different aspects, and (iii) accounting for influencing factors, such as different treatment approaches, that may impact AD and psoriasis severity, which make it challenging to compare findings across studies. Overall, we anticipate that the insights gained from these discussions will increase the likelihood of biomarkers being effectively applied in real-world settings, to ultimately improve outcomes for people with AD and psoriasis.

BIOSKIN: A Protocol for the Copenhagen Translational Skin Immunology Biobank and Research Programme.

INTRODUCTION: Psoriasis, atopic dermatitis and contact dermatitis are common chronic inflammatory skin diseases that have a significant impact on individuals and society. METHODS AND ANALYSIS: The Copenhagen Translational Skin Immunology Biobank and Research Programme (BIOSKIN) is a translational biobank and research study that aims to prospectively collect high-quality biological samples and clinical data from 3000 patients with psoriasis, atopic dermatitis and contact dermatitis over a minimum period of 5 years. The longitudinal open design allows participants to enter and leave the study at different time points depending on their disease and treatment course. At every visit, the investigator collects biological samples, conducts interviews and assembles self-reported questionnaires on disease-specific and general health-related information. Clinical examination and biological sampling will be conducted at enrolment, during and after disease flare, before and after initiation of new treatment and at least once per year. The clinical examination includes dermatological verification of diagnosis, evaluation of disease severity and detailed information on phenotype. The biological samples include blood and when accessible and relevant, skin biopsies, tape strips and skin swabs. The data collected will undergo rigorous statistical analysis using appropriate analytical methods. As of December 2023, 825 patients have been enrolled in the study. ETHICS AND DISSEMINATION: The study is approved by the Scientific Ethical Committee of the Capital Region (H-21032986) and the Danish Data Protection Agency. Results will be published in peer-reviewed scientific journals and presented at national and international conferences.

Does Systemic Anti-Psoriatic Treatment Impact the Risk of Cardiovascular Disease? A Review Over Cardiovascular Imaging Studies.

Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as the outcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.

In-Depth Proteomic Map of Innate Lymphoid Cells from Healthy Human Skin and Blood.

Innate lymphoid cells (ILCs) are essential players in the skin-associated immune system, nevertheless little is known about their proteomes and proteomic diversity. In this study, we describe about 6,600 proteins constitutively expressed by ILC2s and ILC3s from healthy human skin and blood using state-of-the-art proteomics. Although the vast majority of proteins was expressed by both ILC subsets and in both compartments, the skin ILC2s and ILC3s were more distinct than their counterparts in blood. Only skin ILC3s expressed uniquely detected proteins. Our in-depth proteomic dataset allowed us to define the cluster of differentiation marker profiles of the ILC subsets, explore distribution and abundance of proteins known to have immunological functions, as well as identify subset-specific proteins that have not previously been implicated in ILC biology. Taken together, our analyses substantially expand understanding of the protein expression signatures of ILC subsets. Going forward, these proteomic datasets will serve as valuable resources for future studies of ILC biology.

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies.

BACKGROUND: Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis. METHODS: We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226). RESULTS: We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (n = 313), followed by lesional versus healthy skin (n = 185), blood from patients with psoriasis versus blood from healthy individuals (n = 140), and non-lesional versus healthy skin (n = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis. CONCLUSION: Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research.