Background: Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus, although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their associations with AD severity, barrier function, and epidermal gene expression in the first US early-life cohort of children with AD, the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH). Methods: The biofilm propensity of staphylococcal isolates was assessed by crystal violet assays. Gene expression of filaggrin and antimicrobial alarmins S100A8 and S100A9 was measured in keratinocyte RNA extracted from skin tape strips. Staphylococcal biofilms sampled from MPAACH skin were visualized using scanning electron microscopy. Results: Sixty-two percent of staphylococcal isolates (sampled from 400 subjects) formed moderate/strong biofilms. Sixty-eight percent of subjects co-colonized with both staphylococcal species exhibited strains that formed cooperative mixed-species biofilms. Scanning electron microscopy verified the presence of staphylococcal biofilms on the skin of MPAACH children. Staphylococcus aureus strains showing higher relative biofilm propensity compared with S epidermidis were associated with increased AD severity (P = .03) and increased lesional and nonlesional transepidermal water loss (P = .01, P = .03). Conclusions: Our data suggest a pathogenic role for S aureus biofilms in AD. We found that strain-level variation in staphylococcal isolates governs the interactions between | 303 GONZALEZ Et AL.

No abstract

Background: Children with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity. Objective:We sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity. Methods:We studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations. MPAACH is a paediatric AD cohort, aged 1-2, recruited through hospital/community settings between 2016 and 2018. We analysed these groupings' associations with AD biomarkers: skin FLG, S100A8 and S100A9 expression, total IgE, TEWL and AD severity.Results: An unbiased machine learning approach revealed five allergen clusters. The most common cluster (N = 131), SPT PEP, had sensitization to peanut, egg and/or pets. Three low prevalence clusters, which included children with allergen sensitization other than peanut, egg or pets, were combined into SPT Other . SPT NEG included children with no sensitization(s). SPT PEP children had higher median non-lesional TEWL (16.9 g/m 2 /h) and IgE (90 kU/L) compared with SPT OTHER (8.8 g/m 2 /h and 24 kU/L; p = .01 and p < .001) and SPT NEG (9 g/m 2 /h and 26 kU/L; p = .003 and p < .001). SPT PEP children had lower median lesional (0.70) and non-lesional (1.09) FLG expression compared with SPT OTHER (lesional: 0.9; p = .047, non-lesional: 1.78; p = .01) and SPT NEG (lesional: 1.47; p < .001, non-lesional: 2.21; p < .001). There were no differences among groupings in S100A8 or S100A9 expression. Conclusions and clinical relevance:In this largely clinic-based cohort of young children with AD, allergic sensitization to peanut, egg, cat or dog was associated with more severe disease and skin barrier function but not markers of cutaneous inflammation. These data need replicating in a population-based cohort but may have important implications for understanding the interaction between AD and allergic sensitization. | 667 SHERENIAN Et Al.

No abstract

No abstract

No abstract

RATIONALE: IgE plays a central role in the development of allergic rhinitis (AR). Although endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of allergic airway diseases, such as asthma, its role in AR is poorly studied. METHODS: Real-time PCR, immunohistochemistry and western blot analysis were applied to detect the expression of ER stress markers GRP78, CHOP, ATF6a, XBP-1, its splice variant (sXBP-1), and p-eIF2a in nasal tissue samples from control subjects and AR patients. Immunostaining of serial tissue sections were performed to detect the cellular sources of GRP78 and CHOP. Nasal explant tissues from AR patients were cultured ex vivo and secretion of IgE to culture supernatants were measured. RESULTS: Compared to control tissues, the mRNA and protein expression of ER stress markers GRP78 , CHOP, ATF6a, XBP-1, sXBP-1, and p-eIF2a were all significantly up-regulated in nasal tissues from AR patients compared to control tissues as detected by RT-PCR, immunohistochemistry and western blot analysis. The immunoreactivity of GRP78 and CHOP were mainly located in CD138 + plasma cells in lamina propria in nasal tissues. The numbers of GRP78 and CHOP positive cells correlated with the numbers of plasma cells and IgE + plasma cells. In addition, after treated with 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, the mRNA and protein levels of GRP78, CHOP, ATF6a, XBP-1, sXBP-1, and p-eIF2a were down-regulated in nasal explant tissues and IgE levels were reduced in culture supertanants. CONCLUSIONS: The ER stress may be invovled in the regulation of local IgE secretion from plasma cells in AR patients.

Local anaesthetics (LA) are often suspected as possible causes of allergic reactions but the incidence of adverse events (including allergy) is low. The incidence of immediate reactions to LA in patients with clonal mast cell disorders (MCD) is unknown. The purpose of this study was to investigate the true incidence of LA allergy in patients with (MCD). METHODS: In the period 2012-2018, a total of 432 patients (186 women/ 246 men; median age 53 years, range 17-86 years) were underwent to bone marrow biopsy (BMB) with LA in suspicious of MCD. In case of positive history of LA allergy , an allergological work-up was made (skin prick test, intradermal test and subcutaneous provocation). All 432 patients were underwent to BMB in association with LA, chosen based on clinical history and allergological test. MCD was diagnosed in 180 patients (41.7%). 5 patients of them suffered from important mediator symptoms and for reasons were premedicated before BMB with steroids and antiH1. RESULTS: 5 of 180 (2%) patients with MCD and 7 of 252 (3.9%) patients without MCD had history of allergy to LA. All these patients had negative allergological tests for LA. All patients with MCD tolerated BMB with LA as well as all the patients without MCD. Only 1 patients with MCD had vagal hypotension during BMB. CONCLUSIONS: MCD is not a risk factor for allergy to LA. Therefore the use of LA in patients with MCD is safe. Premedication is not necessary exept in patients with history of important mediator symptoms.