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Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable "alternative" option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not "class‐related," as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities. [ABSTRACT FROM AUTHOR]

Adult patients, with moderate or severe AD, were randomized 1:1 to receive mepolizumab or placebo every 4 weeks on day 1, week 4, week 8, and week 12 of the 16-week treatment period. For the IGA endpoint, only 2 of 18 (11%) patients receiving mepolizumab and none of the 16 patients receiving placebo achieved treatment success at Week 16. This study did not show clinical improvement in patients with moderate/severe AD while receiving mepolizumab despite the observed blood eosinophils reduction and mepolizumab concentrations being consistent with that observed in patients with severe asthma. [Extracted from the article]

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes. [ABSTRACT FROM AUTHOR]

Allergies are typically endemic, complex and heterogeneous diseases with a high impact at quality of life. Mechanistically, type 2 immune responses involving eosinophil and basophil granulocytes, mast cells and humoral factors such as IgE are key drivers of allergic diseases. Fighting allergic diseases knows three strategies: prevention, symptomatic and causative therapy. While remarkable progress was made in understanding molecular events in allergies as a prerequisite for effective prevention and desensitization, this review article focuses on the most efficient symptomatic treatments—that is using more and more specific antibodies neutralizing particular immune pathways. We highlight and classify recent and upcoming developments in the three prototype chronic allergic diseases allergic asthma, chronic spontaneous urticaria and atopic eczema. In all three examples, biologics such as dupilumab or omalizumab become reliable and efficient therapeutic options. Finally, we give an outlook how a diagnostic and therapeutic workflow might look like in the near future for these three major burdens of society. [ABSTRACT FROM AUTHOR]

LAT1-specific inhibitor is effective against T cell-mediated allergic skin inflammation LAT1 inhibition alleviates T cell-dependent dermatitis by suppressing glycolysis/OXPHOS-cyclin/CDK axis in Th2 cells. LAT1 substrate depletion also impaired OXPHOS and glycolysis (Figure S3), implying that the JPH203-mediated down-regulation of OXPHOS and glycolysis is caused by amino acid starvation. The LAT1-glycolysis/OXPHOS-cyclin/CDK axis could provide an advantage to T cells for the adaptive tuning of cytokine production and cell proliferation in response to nutrient shortages (either glucose or amino acids). [Extracted from the article]

Background: Skin desquamation is facilitated by serine proteases KLK5 and KLK7, which are tightly regulated by lympho‐epithelial Kazal‐type related inhibitor (LEKTI). LEKTI itself is controlled through degraded by mesotrypsin. Here, we sought to determine whether LEKTI exonic mutations associated with atopic dermatitis (AD) affect the protease inhibitory activity of LEKTI or its susceptibility to mesotrypsin degradation. Methods: The inhibitory activities of the LEKTI domain 4 (D4) and D6 WT and AD‐associated mutants on the enzyme activities of KLK5 and KLK7 were compared using fluorogenic substrates. A keratinocyte cell culture system using HaCat cells was established to assess the role of D6 WT and D386N on triggering inflammation via the induction of thymic stromal lymphopoietin (TSLP). A degradation assay was used to assess the susceptibility of D4 and D6 mutants to mesotrypsin degradation. Results: Enzymatic assays revealed that the D6 D386N mutation affected the inhibitory activity of LEKTI on KLK5 but not KLK7. Other exonic mutations on D6 (N368S, V395M, and E420K) and D4 (R267Q) did not alter LEKTI inhibition. The D386N mutation disrupted the role of D6 in suppressing TSLP induction by KLK5 in HaCat cells. Although WT D4 is more susceptible to mesotrypsin degradation than WT D6, the D4 R267Q mutant was more resistant to mesotrypsin degradation, whereas the D6 E420K mutant showed enhanced mesotrypsin‐mediated degradation. Conclusion: Exonic mutations in D6, which previously have been associated with AD, may cause a disruption of inhibitory activity on KLK5 or enhance the degradation by mesotrypsin. [ABSTRACT FROM AUTHOR]

Background: Probiotic supplementation to mothers and/or their term‐born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. Methods: This sub‐study was an a priori secondary outcome of the ProPrems multi‐center, double‐blind, placebo‐controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. Results: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI −8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. Conclusion: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed. [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. Objective: To study the effect of 16‐week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate‐severe AD in daily practice. Methods: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen‐week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI‐50 (Eczema Area and Severity Index) or EASI‐75, as well as patient‐reported outcomes measures (Patient‐Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty‐one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). Results: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult‐to‐treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI‐50 and EASI‐75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity‐related serum biomarkers (TARC, PARC, periostin, and IL‐22), eotaxin‐1, and eotaxin‐3 significantly decreased. Conclusion: Treatment with dupilumab significantly improved disease severity and decreased severity‐related serum biomarkers in patients with very difficult‐to‐treat AD in a daily practice setting. [ABSTRACT FROM AUTHOR]

Background: New insights into immune cells could contribute to treatment and monitoring of atopic disease. Because nongenetic factors shape the human immune system, we here studied these immune cells in a large cohort with atopic children with adjustment for prenatal and postnatal confounders. Methods: Information on atopic dermatitis, inhalant‐ and food‐allergic sensitization, asthma lung function scores was obtained from 855 10‐year‐old children within the Generation R cohort. 11‐color flow cytometry was performed to determine CD27+ and CD27−IgG+, IgE+ and IgA+ memory B cells, Th1, Th2, Th17, and Treg‐memory cells from venous blood. Associations between any atopic disease, the individual atopic diseases, and immune cell numbers were determined. Results: Children with any atopic disease had higher Th2, Treg, Treg‐memory, and CD27+IgA+ memory B‐cell numbers compared to children without atopic disease. When studying the individual diseases compared to children without the individual diseases, children with atopic dermatitis, inhalant‐, and food‐allergic sensitization had higher memory Treg cell numbers 12.3% (95% CI 4.2; 21.0), (11.1% (95% CI 3.0; 19.8), (23.7% (95% CI 7.9; 41.8), respectively. Children with food‐allergic sensitization had higher total B and CD27+IgA+ memory B‐cell numbers (15.2% [95% CI 3.2; 28.7], 22.5% [95% CI 3.9; 44.3], respectively). No associations were observed between asthma and B‐ or T‐cell numbers. Conclusion: Children with any atopic disease and children with inhalant‐ and food‐allergic sensitization or atopic dermatitis had higher circulating memory Treg cells, but not higher IgE+B‐cell numbers. The associations of higher Treg and CD27+IgA+ B‐cell numbers in children with food‐allergic sensitization are suggestive of TGF‐β‐mediated compensation for chronic inflammation. [ABSTRACT FROM AUTHOR]

Background: The hygiene hypothesis proposes that reduced exposure to infectious agents in early life would explain the increase of allergic and autoimmune diseases observed over the past decades in high‐income countries. Methods: We conducted a matched case‐control study on incident atopic dermatitis (AD). Cases were 426 outpatient children with a first diagnosis of incident AD. Controls were 426 children attending a pediatric/dermatological visit for nonatopic disorders matched to cases (1:1). Particular attention was paid to the time elapsed between the markers of microbial exposure and disease onset, and we considered for controls the same time window of exposures from birth as his/her matched case. Odds ratios (ORs) were computed using multivariable conditional logistic regression models, according to center, sex, age, and period of enrollment, and including as potential confounders a family history of any allergy in parents, type of delivery, having siblings, keeping pets, age at weaning, and having had ≥4 infections. Results: The OR of AD first occurrence was 0.35 (P‐value =.039) for children who had experienced ≥4 infections compared with those with no infections. A decreasing trend in risk was observed with increasing number of siblings (P‐value =.023), the protective effect reaching about 40% for children with 2 or more siblings (OR = 0.62; P‐value =.048). Pet keeping, in particular daily contact with dogs, was inversely associated with AD risk (OR = 0.40; P‐value =.004). Conclusions: These results support the hygiene hypothesis in its broad sense. Early‐life environmental exposures, including pathogens and commensals, act as "microbes contact carriers" influencing immune system balance early in life. [ABSTRACT FROM AUTHOR]

Eczema herpeticum (EH) is a severe and widespread viral skin infection caused by herpes simplex virus 1 (HSV-1), which particularly affects patients with atopic dermatitis (AD) who have a more severe course of the disease, higher allergen sensitization, and greater Th2 polarization.[[1]] The condition has been named ADEH (AD complicated by EH). Our study is the first to show specific IgE against HSV-1 in ADEH patients sera and it provides preliminary evidence of an increased type I and type IV hypersensitivity response to HSV-1 in these patients. A major allergen has been defined as one to which more than 50% of the sera of patients containing specific IgE to a specific allergenic source react. SP S13 sp Here, we showed that especially the viral proteins gD and VP22 were widely recognized by IgE from the ADEH patients sera. [Extracted from the article]

Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)‐driven disease. Interleukin (IL)‐4 and IL‐13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor‐associated signal transduction machinery such as Janus kinases. Recently, IL‐13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL‐4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL‐13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL‐13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex inflammatory disorder with multiple interactions between genetic, immune and external factors. The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome. The exposome spans multiple domains from population to molecular levels and, in combination with genetic factors, holds the key to understanding the phenotypic diversity seen in AD patients. Exposomal domains are categorized into nonspecific (human and natural factors affecting populations), specific (eg humidity, ultraviolet radiation, diet, pollution, allergens, water hardness) and internal (cutaneous and gut microbiota and host cell interaction) exposures. The skin, as the organ that most directly interacts with and adapts to the external environment, is a prime target for exploration of exposomal influences on disease. Given the well‐recognized physical environmental influences on AD, this condition could be much better understood through insightful exposomal research. In this narrative review, we examine each domain in turn, highlighting current understanding of the mechanisms by which exposomal influences modulate AD pathogenesis at distinct points in time. We highlight current approaches to exposome modification in AD and other allergic disease and propose future directions for exposome characterization and modification using novel research techniques. [ABSTRACT FROM AUTHOR]

Background: The aim was to study the association between allergic multimorbidity and adult‐onset asthma considering the number of allergic diseases and the age effect. Methods: We used population‐based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30‐93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self‐completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity. Results: A total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min‐max) 53 (11, 31‐71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult‐onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52‐2.49], 2.87 [2.19‐3.77], and 4.26 [3.07‐5.90], respectively. The association between adult‐onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51‐4.94], 2.44 [1.74‐3.42], and 1.68 [1.04‐2.71]) in subjects < 50 years, 50‐62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002). Conclusions: Adult‐onset asthma was positively associated with the number of allergic diseases, and this association decreases with age. [ABSTRACT FROM AUTHOR]

Background: The prevention of food allergy is a key priority for reducing the burden of allergic disease. Environmental exposures modulate the risk of developing food allergy and some of this may be mediated by the infants' developing microbiome. However, the role of potentially protective environmental exposures, such as pet ownership, is largely uninvestigated with respect to food allergy. Methods: We performed a secondary cohort analysis in the Enquiring About Tolerance (EAT) study, which enrolled 1303 three‐month infants onto a randomized trial to prevent food allergy. A survey elicited domestic animal ownership and participants were examined for atopic dermatitis (AD) at enrolment. Sensitization to foods and aeroallergens were elicited by skin and serum testing at 3, 12 and 36 months. Food allergy status was determined by double‐blind placebo‐controlled food challenges between 1 and 3 years. Results: Food allergy was diagnosed amongst 6.1% (68/1124) of participants with complete data. No significant relationships were demonstrated between food allergy and caesarean delivery, infections or antibiotic exposure in early life. After adjusting for familial atopic disease, maternal dog/cat sensitization and participant AD, living with dogs was associated with a 90% reduction in the odds of infants developing food allergy (adjusted odds ratio (aOR) 0.10 (confidence interval (CI) 0.01‐0.71), P = 0.02). None of the 49 infants living with at least two dogs developed food allergy, suggesting a dose‐response relationship (each dog owned aOR 0.12 (CI 0.02‐0.81), P = 0.03). No relationship was demonstrated between owning dogs or cats and the development of AD. Conclusion: Dog ownership in infancy may prevent food allergy. [ABSTRACT FROM AUTHOR]

Background: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3‐ to 15‐month‐olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA. Methods: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow‐up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets. Results: 205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1‐h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P‐values were between 0.01 and 0.05 for younger age, non‐white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive. Conclusions: Key factors associated with PNA in this high‐risk population included lack of breastfeeding, age, and greater Ara h2 and peanut‐specific IgE, which can be used to prognosticate outcomes. [ABSTRACT FROM AUTHOR]

Background: miR‐10a‐5p has been shown to regulate cancer cell proliferation and invasiveness and endothelial cell inflammatory responses. The function of miR‐10a‐5p in the skin has not been previously studied. The aim of the current study was to examine miR‐10a‐5p expression, regulation, and function in keratinocytes (KCs) in association with atopic dermatitis (AD). Methods: The expression of miR‐10a‐5p and its target genes was analyzed using RT‐qPCR, mRNA array analysis, in situ hybridization, and immunofluorescence. The transfection of miRNA mimics, cell cycle distribution analysis, and luciferase assays was used to study miR‐10a‐5p functions in human primary KCs. Results: miR‐10a‐5p was found to be upregulated in lesional skin from patients with AD and in proliferating KCs. Array and pathway analysis of IL‐1β‐stimulated KCs revealed that miR‐10a‐5p inhibited many genes that affect cell cycle progression and only a few inflammation‐related genes. Accordingly, fewer cells in S‐phase and reduced proliferation were detected as characteristics of miR‐10a‐5p‐transfected KCs. The influence of miR‐10a‐5p on cell proliferation was also evident in KCs induced by AD‐related cytokines, including IL‐4, IL‐17, and IL‐1β, as measured by the capacity to strongly suppress the expression of the proliferation marker Ki‐67. Among AD‐related putative direct target genes, we verified hyaluronan synthase 3, a damage‐associated positive regulator of KC migration and proliferation, as a direct target of miR‐10a‐5p. Conclusions: miR‐10a‐5p inhibits KC proliferation and directly targets hyaluronan synthase 3 and thereby may modulate AD‐associated processes in the skin. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is being recognized as a major cofactor in atopic diseases such as atopic dermatitis, chronic rhinosinusitis with nasal polyps, and asthma. The understanding of the relationship between S aureus virulence factors and the immune system is continuously improving. Although the precise mechanism of the host's immune response adaptation to the variable secretion profile of S aureus strains continues to be a matter of debate, an increasing number of studies have reported on central effects of S aureus secretome in allergy. In this review, we discuss how colonization of S aureus modulates the innate and adaptive immune response, thereby predisposing the organism to allergic sensitization and disrupting immune tolerance in the airways of patients with asthma and chronic rhinosinusitis with nasal polyps. Next, we provide a critical overview of novel concepts dealing with S aureus in the initiation and persistence of chronic rhinosinusitis with nasal polyps and asthma. The role of the S aureus serine protease‐like proteins in the initiation of a type 2 response and the contribution of the IL‐33/ST2 signaling axis in allergic responses induced by bacterial allergens are discussed. [ABSTRACT FROM AUTHOR]

Background: Many skin and mucosal inflammatory disorders, such as atopic dermatitis, have been associated with an impaired epithelial barrier function, which allows allergens, pollutants, or microbes to enter the tissue and activate the immune response. The aim of this study was to establish a method to directly assess in vivo the epidermal barrier function by electrical impedance (EI) spectroscopy. Methods: Mice epidermal barrier was damaged by epicutaneous application of proteases and cholera toxin and by tape stripping. EI and transepidermal water loss (TEWL) were measured before and after the application. Additionally, histological analysis, immunofluorescence staining, and RT‐PCR were performed on skin biopsies to evaluate the epithelial barrier. Results: A few hours after papain application, a dose‐dependent reduction of EI was detected, reflecting the decreased barrier function. At the same time, an increase of TEWL was observed, with a significant negative correlation with EI, demonstrating that EI changes were directly linked to barrier defects. Twenty‐four and 48 hours after the treatment, EI starts to increase to background levels, indicating tissue healing and restoration of skin barrier. Barrier disruption was confirmed by histological analysis showing an impaired stratum corneum and higher cellular infiltration after papain application. In addition, immunofluorescence staining and RT‐PCR showed downregulation of molecules involved in the barrier function, such as filaggrin, occludin, and claudin‐1, and mRNA levels of filaggrin, loricrin, and involucrin. Comparable results were observed after tape stripping and cholera toxin treatment. Conclusion: Electrical impedance spectroscopy is a rapid and reliable diagnostic tool to detect skin barrier defects. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is one of the most common skin diseases with a multifactorial etiology. Mutations leading to loss of skin barrier function are associated with the development of AD with group 2 innate lymphoid cells (ILC2) promoting acute skin inflammation. Filaggrin‐mutant (Flgft/ft) mice develop spontaneous skin inflammation accompanied by an increase in skin ILC2 numbers, IL‐1β production, and other cytokines recapitulating human AD. Here, we investigated the role of ILC2, effector cytokines, inflammasome activation, and mast cell function on the development of chronic AD‐like inflammation in mice. Methods: Mice with a frameshift mutation in the filaggrin gene develop spontaneous dermatitis. Flgft/ft mice were crossed to cell‐ or cytokine‐deficient mouse strains, or bred under germ‐free conditions. Skin inflammation was scored, and microbiome composition was analyzed. Skin protein expression was measured by multiplex immunoassay. Infiltrating cells were analyzed by flow cytometry. Results: Wild‐type and Flgft/ft mice significantly differ in their microbiome composition. Furthermore, mutant mice do not develop skin inflammation under germ‐free conditions. ILC2 deficiency did not ameliorate chronic dermatitis in Flgft/ft mice, which was also independent of IL‐4, IL‐5, IL‐9, IL‐13, IL‐17A, and IL‐22. Inflammation was independent of NLRP3 inflammasome activation but required IL‐1β and IL‐1R1‐signaling. Mechanistically, IL‐1β promoted hyperactivation of IL‐1R1‐expressing mast cells. Treatment with anti‐IL‐1β‐antibody alleviated dermatitis exacerbation, while antibiotic intervention ameliorated dermatitis in neonatal mice but not in adults with established inflammation. Conclusions: In summary, we identified a critical role for the microbiome and IL‐1β mediating chronic inflammation in mice with an impaired skin barrier. [ABSTRACT FROM AUTHOR]

Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. In humans, they reported that a mixture of minimal-length peptides, representing the major T-cell epitopes of allergen, is sufficient to induce specific tolerance in T cells and successful allergen-specific immunotherapy. [Extracted from the article]

Keywords: atopic dermatitis; emollients; food allergens EN atopic dermatitis emollients food allergens 1121 1122 2 04/04/23 20230401 NES 230401 We read, with great interest, Ní Chaoimh et al.'s[1] article in the August 2022 issue of the I Allergy i . However, oat-derived ingredients in personal care products can cause immediate- and delayed-type hypersensitivity reactions.[5] It was shown that children with AD have a high oat sensitization, oat atopy patch tests, and skin-prick tests were positive in 14.6% and 19.2% of cases, respectively.[6] In addition, an association between oat sensitization and the repeated applications of oat-containing skin care products was found. When they are dried, extracted, and filtered, protein-free extracts, which are active ingredients in emollient-plus products, are produced.[8] We want to highlight the importance of choosing bland and food allergen-free skin care products. [Extracted from the article]

Multi-omics analyses implicate EARS2 in the pathogenesis of atopic dermatitis In conclusion, we used various omics profiles to construct a prediction model of AD and found several potentially crucial factors for the prediction, including the host expression of I EARS2 i . Keywords: atopic dermatitis; EARS2; multi-omics analysis; prediction model EN atopic dermatitis EARS2 multi-omics analysis prediction model 2602 2604 3 07/19/21 20210801 NES 210801 In recent years, omics data for studies on atopic dermatitis (AD) have become more available. [Extracted from the article]

Keywords: Emollient; atopic eczema; infancy EN Emollient atopic eczema infancy 2641 2643 3 07/19/21 20210801 NES 210801 Abbreviations FA food allergy FLG filaggrin gene AD atopic dermatitis TEWL transepidermal water loss BEEP Barrier Enhancement for Eczema Prevention PreventADALL Preventing Atopic Dermatitis and Allergies Atopic dermatitis/Eczema (AD) is the most common chronic inflammatory skin disease affecting up to 30% of children. It is unknown whether emollient usage may promote barrier integrity and affect the interplay between barrier impairment, skin inflammation, and ultimately prevent atopic dermatitis development. Thus, skin barrier dysfunction due to environmental factors and genetic predisposition paired with skin inflammation is linked to AD and consequently food sensitization, food allergy (FA), and progression of the allergic disease complex (Figure 1).1 The importance of barrier integrity for AD is supported by filaggrin (FLG). [Extracted from the article]

Keywords: allergy diagnosis; atopic dermatitis; challenge tests; complementary feeding; food allergy; pediatrics; prevention; weaning EN allergy diagnosis atopic dermatitis challenge tests complementary feeding food allergy pediatrics prevention weaning 1592 1594 3 05/17/21 20210501 NES 210501 Oral tolerance induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.1,2 OTI to peanut is highly effective in a high-risk population with an 81% relative risk ration (RRR) to peanut allergy.3 OTI also reduced egg allergy in the general population in a per-protocol analysis.1 These published RCT findings have changed practice and many governmental and allergy societies now recommend introducing peanut in infancy; some suggest that other foods, such as well-cooked egg, are also introduced. Commencing multiple food OTI at 4 months of age has no detrimental effect on established breastfeeding.6,7 All children may adopt a diverse weaning diet,8 including allergenic foods such as well-cooked egg and peanut, as soon as weaning commences. Allergy diagnosis, atopic dermatitis, challenge tests, complementary feeding, food allergy, pediatrics, prevention, weaning. [Extracted from the article]

Remarkably, our results are comparable with those of clinical and real-life studies, although exclusively patients with severe AD were eligible to get dupilumab therapy. SP S5-S11,S14,S15 sp Already one month after initiating dupilumab therapy, 60% reported that AD did not or minimally affected their quality of life (Figure 1). Keywords: atopic dermatitis; dupilumab; epidermal barrier; interleukin-13; type 2 inflammation EN atopic dermatitis dupilumab epidermal barrier interleukin-13 type 2 inflammation 1268 1270 3 04/14/21 20210401 NES 210401 The pathogenesis of atopic dermatitis (AD), a common chronic inflammatory skin disease, is based on a genetic predisposition that determines both skin barrier function and type 2 immune reaction.1,2 SP ,S1-S4 sp Type 2 cytokines may further impair the epidermal barrier and trigger AD inflammation.1 Therapy with dupilumab that inhibits the action of interleukin (IL)-4 and IL-13 by blocking the shared receptor results in a rapid improvement of symptoms, clinical signs, and quality of life in AD patients.3 SP ,S5-S11 sp Transcriptome analyses of skin samples suggest that it affects mRNA expression of genes related to type 2 inflammation, T helper (Th)17/Th22 pathways, dendritic cells, epidermal barrier, and lipid metabolism.4,5 SP ,S12-S13 sp This study aimed at assessing the efficacy and safety of dupilumab therapy in patients with AD referred to a tertiary center and at investigating the effect of dupilumab on both inflammation and epidermal barrier by applying immunofluorescence techniques. [Extracted from the article]

Background: Autoreactive immunoglobulin E (IgE) antibodies to self-peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well-characterized patients with AD and controls (1.2-88.9 years)., Methods: Atopic dermatitis patients were sub-grouped in AD with comorbid Type-2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type-2 diseases ("atopic controls," n = 52) and non-atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples., Results: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD-patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean-section and diversity of domestic pets., Conclusions: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration., (© 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)-13 is a cytokine that acts as a driver of immune dysregulation, skin-barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL-13 with high affinity, thereby inhibiting subsequent downstream IL-13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate-to-severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index-75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient-reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL-13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate-to-severe AD., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: While the microbiome is increasingly seen as a targetable contributor to atopic dermatitis (AD), questions remain as to whether the dysbiosis is secondary to diseased skin or if it predates symptom onset. Previous work has evaluated how the skin microbiome changes with age and established the influence of factors like delivery mode and breastfeeding on global microbiome diversity. However, these studies were unable to identify taxa which predict subsequent AD., Methods: Skin swab samples were collected from the first week of life for 72 children in the neonatal intensive care unit (NICU) at a single site hospital. Participants were followed for 3 years to determine their health status. We applied shotgun metagenomic sequencing to assess the microbiome differences between 31 children who went on to develop AD and 41 controls., Results: We identified that subsequent development of AD was associated with differential abundance of several bacterial and fungal taxa as well as several metabolic pathways, each of which have been previously associated with active AD., Conclusions: Our work provides evidence of reproducibility for the previously reported dysbiotic signatures predating AD onset while also expanding prior findings through the first use of metagenomic assessment prior to AD onset. While extrapolation of our findings beyond the pre-term, NICU cohort is limited, our findings add to the evidence that the dysbiosis associated with AD pre-dates disease onset rather than reflect a secondary consequence of skin inflammation., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

To the Editor, We were excited to read the correspondence from Dr. Fehr et al[1] regarding our recent manuscript describing immunological endotypes in rural and urban children with atopic dermatitis (AD) in South Africa[2] and are delighted to respond on this very important and long overdue topic of study. Expression of T SB H sb 17-related genes in adult African American AD lesional skin was higher than that seen in African American AD non-lesional and healthy skin, but was lower than that observed in European American AD skin.[4] Our studies showed lower levels of circulating T SB H sb 17-associated cytokines in South African AmaXhosa children with AD compared with healthy South African AmaXhosa children.[2] In contrast, Fehr et al highlighted one of their own studies that showed higher levels of T SB H sb 17 cytokines in adult Tanzanian AD patients compared with adult Swiss AD patients. [Extracted from the article]

Evidence for different immune signatures and sensitization patterns in sub-Saharan African vs. central European atopic dermatitis patients. In our work, however, we identified higher serum levels of pro-inflammatory Th1/Th17 cytokines in Tanzanian AD patients compared to Swiss AD patients.[5] Besides the divergence between the immune signatures, environmental exposures which can translate to sensitizations/allergies considerably differ among AD patients depending on their origin and environment. We have read with great interest the study of Lunjani et al.[1] in which they investigated the impact of diverse environmental and socioeconomic factors on atopic dermatitis (AD) immune endotypes in children living in South Africa. [Extracted from the article]

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid‐associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis. [ABSTRACT FROM AUTHOR]

The change in the prevalence of wheeze, eczema and rhino-conjunctivitis among Japanese children: Findings from 3 nationwide cross-sectional surveys between 2005 and 2015 Among 6- to 8-year-olds, although the prevalence of children with wheeze, eczema or both decreased between 2005 and 2015, the overall proportion with any allergic disease was similar (33.7% and 34.7%), due to the increase in children with rhino-conjunctivitis only (8.5%-12.5%). Similarly, among 13- to 15-year-olds, the increase in rhino-conjunctivitis only (15.3%-20.3%) or with comorbid wheeze or eczema (5.2%-6.5%) resulted in an overall increase in children with any allergic disease (31.9%-36.5%). It has been speculated that the plateau in prevalence is showing that the saturation level, determined by the genetic composition of the population, has been achieved.[4] However, we found that the prevalence of rhino-conjunctivitis was still rising, in contrast with the change in wheeze or eczema. [Extracted from the article]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. [ABSTRACT FROM AUTHOR]

The article discusses a 2019 study on the effect of the topical calcineurin inhibitor tacrolimus on skin microbiome in the skin disease atopic dermatitis (AD) of Thai subjects. Results show that skin microbiome dysbiosis is an important feature of AD in Thais, and that tacrolimus positively impacts skin microbiome in AD. Also noted is the potential of tacrolimus in alleviating AD in the future.

The article discusses a study on the skin inflammation increase in atomic dermatitis (AM) by way of the inhibitory receptor (IR) CD300a. Results suggested a down-regulatory role for CD300a in AD inflammation as in previous demonstrations on other allergic and nonallergic diseases, and their murine models. Also noted is the possible use of CD300a-specific activation as a support in AD anti-inflammatory strategy.

The article offers information on the Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by pruritus, dermatitis at predilection sites, and a positive family history for AD and type I allergies. It mentions many AD patients elevated levels of immunoglobulin E (IgE); and also mentions patients with higher IgE levels benefitted less compared to patients with lower IgE.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893). Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks. Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P = 0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin‐2 (P = 0.008), eotaxin‐3 (P = 0.031), pulmonary and activation‐regulated chemokine (P = 0.016), IgE (P = 0.023), and IL‐13 (P = 0.031). Conclusions: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa. Dupilumab reduced multiple type 2 inflammation biomarkers in nasal secretions and polyp tissues of patients with chronic rhinosinusitis with nasal polyposis, including total IgE and chemoattractants for inflammatory cells Local reductions in type 2 biomarkers were consistent with overall, parallel improvements in nasosinal symptoms and reductions in polypoid tissue These findings suggest that inhibition of IL‐4/IL‐13 signaling via dupilumab‐mediated blockade of IL‐4Rα can suppress underlying inflammation of nasal polyposis, leading to clinical benefits [ABSTRACT FROM AUTHOR]

Background: The effect of exposure to microorganisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases. Methods: In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors, and allergic diseases were collected by questionnaires from birth to 6 years (N = 931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (ie, number of consumed types among 6 types: hard pressed, semipressed, soft, blue, fresh cheese, and cheese from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma, and atopic sensitization at 6 years after adjustment for confounders of atopy. Results: Cheese consumption (vs. nonconsumption) had a significant protective effect on AD (OR = 0.51 [0.29‐0.90], P = 0.02) and FA (OR = 0.32, [0.15‐0.71], P = 0.004), but no effect on atopic sensitization, allergic rhinitis, and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR = 0.64 [0.48‐0.85] per cheese type, P = 0.002; OR = 0.55 [0.33‐0.92], P = 0.02, respectively). Conclusion: Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods. Data from the PASTURE cohort were used to evaluate the effect of cheese consumption at 18 months of age against allergic diseases up to 6 years of age Multivariate analyses adjusted for major confounders showed a protective effect of cheese consumption and variety against atopic dermatitis and food allergy, but not on allergic rhinitis, asthma, and sensitization to allergens. Reverse causality cannot be totally ruled out but is unlikely. Hypothesis: The variety of cheese consumed in early life could influence the immune system, through microbial components and by anti‐inflammatory compounds (short‐chain fatty acids) [ABSTRACT FROM AUTHOR]

The article offers a study predicting disease severity in atopic dermatitis (AD) patients treated with cyclosporin A (CsA). Topics include patients with AD, treated with CsA were included; assessed by Eczema Area and Severity Index (EASI) and serum collected before start of CsA; study showed two patients have notable discrepancies between EASI and predicted EASI scores; and study demonstrates that p‐EASI consisting on serum biomarkers predicts disease severity in AD patients.

Background: Staphylococcus aureus (S. aureus) is frequently detected in the skin of patients with atopic dermatitis (AD), and involved in the flare of AD. There are some evidence‐specific strains of S. aureus affect the severity of AD. However, the mechanism of predominant colonization and the aggravation of dermatitis by certain strains of S. aureus in the patients with AD are still unknown. Objective: To reveal the characteristics of S. aureus from patients with AD (S. aureus‐AD), we analyzed the interaction of S. aureus‐AD and keratinocytes in comparison with those of S. aureus laboratory strains (S. aureus‐stand.). Methods: We stimulated HaCaT cells, keratinocyte cell line, and human epidermal keratinocytes by heat‐killed S. aureus strains, then evaluated immune response of keratinocytes by ELISA, immunofluorescence staining, and flow cytometry. Results: Upon incubation with keratinocytes, three out of four strains of heat‐killed S. aureus‐AD were strongly agglutinated inside the cytoplasm. In the cells, they are located in lysosomes and promoted the secretion of interleukin‐1α (IL‐1α). These reactions were not observed by any of four strains of S. aureus‐stand. and S. epidermidis and were abolished by the treatment of S. aureus with proteinase K. Moreover, the IL‐1α secretion was diminished by the inhibition of Toll‐like receptor 9 (TLR9). Conclusion: S. aureus‐AD accumulates in lysosome of keratinocytes by means of bacterial cell wall proteins and induces IL‐1α via TLR9. Compared to standard S. aureus strains, S. aureus isolated from AD skin are able to induce different innate immune responses. S. aureus from AD skin are internalized into keratinocytes and accumulate in lysosomes with inducing IL‐1α secretion via TLR9. Specific surface proteins of S. aureus from AD skin are responsible for their internalization. [ABSTRACT FROM AUTHOR]

The article offers information on the High‐density lipoprotein (HDL). Topics discussed include HDL suppresses the activation of immune cells,1 including eosinophils; mentions the HDL‐triglyceride content correlated with the inhibitory activity of HDL toward agonist‐induced eosinophil shape change; and also mentions that AD is associated with profound alterations in HDL composition linked to the formation of dysfunctional HDL.

Background: While much is known on childhood atopic diseases, knowledge about persistence of atopic diseases from childhood to adulthood is limited. We therefore aimed to study the clinical course of atopic diseases and type I sensitization prospectively in an unselected cohort of adolescents followed into adulthood. Methods: A cohort of unselected 8th‐grade school children (mean age 14 years) established in 1995 and followed up in 2010 were evaluated with questionnaire, clinical examination, skin prick tests and measurements of specific IgE. Results: The lifetime prevalence of atopic diseases was high and increased significantly from adolescence (31%) to adulthood (57%); particularly allergic rhinitis increased with an incidence rate of 17.5/1000 person‐years. Childhood predictors for adult allergic rhinitis were atopic dermatitis, asthma and asymptomatic sensitization to pollen and house dust mite. Among those with asymptomatic sensitization in adolescence, 53%‐78% developed allergic rhinitis in adulthood. Furthermore, type I sensitization increased significantly from adolescence to adulthood mostly due to increased sensitization to pollen. Type I sensitization was found mainly in those with allergic rhinitis. A high number of adults had oral allergy symptoms due to the high number of birch pollen allergic individuals. Conclusion: Persistence of atopic diseases in adulthood is common, and a high proportion of the adult population is sensitized giving a high prevalence of allergic rhinitis. Many with asymptomatic sensitization in adolescence will develop allergic rhinitis in adult life. The focus should be on prevention of atopic diseases and sensitization already in childhood. The lifetime prevalence of allergic rhinitis increased significantly from adolescence to adulthood. Childhood predictors for adult allergic rhinitis were atopic dermatitis and asthma. Furthermore, more than half with asymptomatic sensitization to pollen and house dust mite in adolescence developed allergic rhinitis in adult life. Type I sensitisation increased significantly from adolescence to adulthood mostly due to increased sensitization to pollen. [ABSTRACT FROM AUTHOR]

Background: Hyper‐IgE syndromes (HIES) are a clinically overlapping, heterogeneous group of inborn errors of immunity characterized by elevated serum IgE level, eosinophilia, atopy, and immune dysregulation. Deficiency of DOCK8 protein is potentially a life‐threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK8 deficiency is critical and should be sought at an early stage to initiate definitive therapy. Methods: Serum samples from patients with DOCK8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression. Results: CXCL10 and TNF‐A were upregulated in DOCK8 patients when compared to AD, possibly contributing toward increased susceptibility to infections and cancer. In contrast, epidermal growth factor (EGF) was significantly downregulated in a subgroup of DOCK8‐deficient and AD patients, while IL‐31 expression was comparable between both DOCK8‐deficient and AD cohorts, possibly contributing toward pruritus seen in both groups. Conclusion: This comprehensive cytokine profile in HIES patients reveals distinctive biomarkers that differentiate between the DOCK8‐deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK8 deficiency vs atopic dermatitis likely reflects disease‐specific perturbations in multiple cellular processes and pathways leading to a predisposition to infections and allergies seen in these patients. These data agree with the role for EGF replacement therapy in EGF‐deficient individuals with AD as well as DOCK8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK8 deficiency from AD allowing early‐targeted treatment options. [ABSTRACT FROM AUTHOR]

All body surfaces are exposed to a wide variety of microbes, which significantly influence immune reactivity within the host. This review provides an update on some of the critical novel findings that have been published on the influence of the microbiome on atopic dermatitis, food allergy and asthma. Microbial dysbiosis has consistently been observed in the skin, gut and lungs of patients with atopic dermatitis, food allergy and asthma, respectively, and the role of specific microbes in allergic disorders is being intensively investigated. However, many of these discoveries have yet to be translated into routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: The use of mesenchymal stem cells (MSCs) has been proposed to treat various autoimmune diseases. However, effective strategies for treating atopic dermatitis (AD) are still lacking, and the mechanisms underlying stem cell therapy remain largely unknown. In this study, we sought to explore potential clinical application of superoxide dismutase 3‐transduced MSCs (SOD3‐MSCs) to experimental AD‐like skin inflammation in in vitro and in vivo and its underlying anti‐inflammatory mechanisms. Methods: SOD3‐MSCs were administered subcutaneously to mice with AD, and associated symptoms and biologic changes were evaluated. Human keratinocytes, mast cells, and murine T helper (Th) 2 cells were cocultured in vitro with SOD3‐MSCs to investigate potential therapeutic effects of SOD3‐MSCs. Results: In mice with AD, SOD3‐MSCs ameliorated AD pathology and enhanced the efficacy of MSC therapy by controlling activated immune cells, by reducing expression levels of proinflammatory mediators in the skin, and by inhibiting the histamine H4 receptor (H4R)‐mediated inflammatory cascade and activation of Janus kinase signal transducer and activator of transcription pathways. Similarly, coculture of SOD3‐MSCs with mast cells, keratinocytes, and Th2 cells effectively dampened H4R‐dependent persistent inflammatory responses by multiple mechanisms. Moreover, we also showed that SOD3 interacts with H4R and IL‐4 receptor α. The functional significance of this interaction could be a markedly reduced inflammatory response in keratinocytes and overall AD pathogenesis, representing a novel mechanism for SOD3's anti‐inflammatory effects. Conclusion: SOD3‐MSCs can be potentially used as an effective and clinically relevant therapy for AD and other autoimmune disorders. (A and B) Proposed mechanism by which SOD3‐MSCs control inflammatory pathways in the skin through regulation of keratinocytes, Th2 cells, and mast cell function. In this study, we demonstrated that SOD3‐MSCs suppress skin inflammation via H4R/IL‐4R‐dependent mechanism, with suppression of multiple proximal pathways in mast cells, keratinocytes, and Th2 cells. [ABSTRACT FROM AUTHOR]