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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), also known as COVID‐19, is a new strain of coronavirus that has not been previously identified in humans. SARS‐CoV‐2 is recognized as a highly contagious respiratory virus with severe morbidity and mortality, especially in vulnerable populations. Being a novel disease, everyone is susceptible, there are no vaccine and no treatment. To contain the spread of the disease, health authorities throughout the world have restricted the social interactions of individuals in various degrees. Allergists, like other physicians, are faced with the challenge of providing care for their patients, while protecting themselves and patients from getting infected, with strategies that are in continuous evolution as states work through the different stages of social distance. Allergist provides care for patients with the most common non‐communicable disease in the world: asthma, allergic rhinitis, food allergy, venom allergy, drug allergy atopic dermatitis, and urticarial syndromes. Some of these diseases are not only considered risk factors for severe reactions but also have symptoms such as cough and sneezing that are in differential diagnosis with COVID‐19. As we move forward, allergy symptoms may prevent patients from working, go to school, or access medical services that increasingly are allowing only asymptomatic individuals. In this review, we will outline how to take care safety of different allergic patients during the pandemic. [ABSTRACT FROM AUTHOR]

Keywords: epidemiology; food allergy; food protein-induced enterocolitis syndrome; FPIES; prevalence EN epidemiology food allergy food protein-induced enterocolitis syndrome FPIES prevalence 1466 1469 4 06/01/20 20200601 NES 200601 Abbreviations FA food allergy FPIES food protein-induced enterocolitis syndrome Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in the esophagus,[1] with the highest disease burden in Western industrialized countries.[2] However, prevalence estimates differ substantially between studies, ranging from as low as 2.3/100 000 in Denmark to as high as 90.7/100 000 in part of the United States.[2] The aforementioned prevalence studies are based on electronic medical records or pathology reports, health insurance claims, patients referred to third level healthcare systems, or subspecialty physician-administered questionnaires;[3] therefore, they tend to reflect specific population prevalence, with consequent potential for socioeconomic and comorbidity selection biases.[2] To the best of our knowledge, no US population-based EoE prevalence estimates have been previously reported. However, the fact that incidence of EoE and its comorbidity is similar to what reported before suggest that this survey-based approach may have captured a population carrying a real EoE diagnosis. Epidemiology, food allergy, food protein-induced enterocolitis syndrome, FPIES, prevalence. [Extracted from the article]

Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate‐severe reactions and as a first‐line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects. [ABSTRACT FROM AUTHOR]

Summary: Eosinophilic oesophagitis (EoE) is a chronic disease associated with significant morbidity that can result in permanent fibrosis and stricture formation. Given the complexity, a multidisciplinary approach is recommended to manage these patients. In the majority of children with EoE not responsive to proton‐pump inhibitor (PPI), inflammation is driven by sensitivity to foods and treatment with an elimination diet can be effective. Foods most commonly identified to trigger EoE in children are milk and wheat, but egg, soy, meats and grains can also be triggers. Foods can be eliminated using a step‐down or step‐up approach. If the goal is to achieve quick remission, elemental diet or six food elimination diets are the most effective. A step‐up approach starting from a 1‐2 food elimination diet and increasing the number of foods based on a personalized dietary approach is recommended if the goal is to achieve remission using the least number of endoscopies and with increased acceptability to the patient. Children with EoE on elimination diets require frequent monitoring of growth and nutrition, as well as screening for symptoms of EoE, allergy and mindfulness regarding psychosocial impact of chronic disease on the family and child. Current research focused on tools to select patients who mostly will benefit from dietary treatment, identify relevant food allergens, obtain oesophageal tissue non‐invasively and induce tolerance will greatly improve the treatment of EoE. [ABSTRACT FROM AUTHOR]

Eosinophilic disorders of the gastrointestinal tract (EGID) are a group of diseases characterized by an eosinophilic inflammation limited to the GI tract. EoE is by far the most common EGID and is an atopic chronic/relapsing eosinophilic inflammation of the esophagus. It is now recognized as an increasingly common cause of esophageal dysfunction, fibrosis, stricture, and food impaction in children and adults. There are globally accepted guidelines for its treatment that are based on the use of proton pump inhibitors (PPI), corticosteroids, and diet. Many clinical trials have been published on the use of biologics in this disease. Non‐EoE‐EGID is a rare, more severe disease. No globally accepted guidelines exist for their treatment and diagnosis. Corticosteroids are at the moment the most effective treatment of those diseases. [ABSTRACT FROM AUTHOR]

Invariant Natural killer T cell (iNKT cells) are a subset of T cells, which are narrowly defined as a T cell lineage expressing a semi-invariant CD1d-restricted T cell Receptors (TCRs) composed by Vα24-Jα18/Vβ11 in human, and Vα14-Jα18/Vβ8,Vβ7, and Vβ2 in mouse. Unlike conventional T cells which recognize peptides bound to highly polymorphic major histocompatibility complex (MHC) class I and II molecules, iNKT cells recognize lipid antigens, such as glycolipids, presented by CD1d, a non-polymorphic non-classical MHC class I molecule. Lipids derived from microbes, tumors, and allergens, as well as self lipids have been shown to be able to activate iNKT cells. Early on, in an immune response, ligation of the iNKT cell TCR leads to rapid and copious secretion of prototypical Th1 and Th2 cytokines. Moreover, like NK cells, iNKT cells express cytotoxic granules, such as perforin and granzyme that polarize upon activation of TCR and are able to kill target cells. Therefore iNKT cells are a very interesting subset of T cells that may bridge the innate and adaptive immune systems. Indeed, iNKT cells can mount specific responses to antigen with cytokine production and cytotoxic activity, however, their TCR evolved to recognize different glycolipid antigens in a conserved manner and to perform innate-like rather than adaptive functions. iNKT cells are now recognized as important players in atopic, autoimmune, infectious diseases, and cancer. [ABSTRACT FROM AUTHOR]

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in westernized countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody-mediated immune responses, there is an increasing recognition of cell-mediated disorders such as eosinophilic esophagitis and food protein-induced enterocolitis. New knowledge is being developed on the pathogenesis of both IgE and non-IgE mediated disease. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if ingestion occurs. However, novel strategies are being studied, including sublingual oral immunotherapy and others with a hope for future. [ABSTRACT FROM AUTHOR]

Although interleukin 13 (IL-13) is an important mediator of asthma and allergic diseases, the molecular mechanisms regulating IL-13 gene expression are not well understood. This study was designed to define the molecular mechanisms governing IL-13 gene expression in T cells. IL-13 expression was examined in human peripheral blood T cells and in the EL-4 T-cell line by enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction. An IL-13 promoter deletion analysis was performed using luciferase-based reporter plasmids transiently transfected into EL-4 cells by electroporation. DNA binding factors were investigated using electrophoretic mobility shift assays. In contrast to IL-4 expression, which required concomitant activation of calcium- and protein kinase C- (PKC-) dependent signalling pathways, PKC activation alone was sufficient for IL-13 protein secretion in mitogen-primed (but not resting) peripheral blood T cells, and for IL-13 mRNA expression and promoter activity in EL-4 T cells. Promoter deletion analysis localized a phorbol 12-myristate 13-acetate (PMA) -sensitive element to a proximal promoter region between − 109 and − 79 base pairs upstream from the IL-13 transcription start site. This promoter region supported the binding of both constitutive and PMA-inducible nuclear factors in gel shift assays. [ABSTRACT FROM AUTHOR]

INTRODUCTION: There are limited data characterizing eating habits among pediatric patients with eosinophilic esophagitis (EoE). We compared eating behaviors in pediatric patients with EoE with healthy controls and assessed the degree of correlation with symptomatology, endoscopic and histologic findings, and esophageal distensibility. METHODS: We conducted a prospective, observational study where subjects consumed 4 food textures (puree, soft solid, chewable, and hard solid) and were scored for eating behaviors including number of chews per bite, sips of fluid per food, and consumption time. Symptomatic, endoscopic, histologic, and esophageal distensibility data were collected for case subjects. RESULTS: Twenty-seven case subjects and 25 healthy controls were enrolled in our study (mean age 11.0 years, 63.5% male). Compared with healthy controls, pediatric patients with EoE demonstrated more chews per bite with soft solid (13.6 vs 9.1, P = 0.031), chewable (14.7 vs 10.7, P = 0.047), and hard solid foods (19.0 vs 12.8, P = 0.037). Patients with EoE also demonstrated increased consumption time with soft solid (94.7 vs 58.3 seconds, P = 0.002), chewable (90.0 vs 65.1 seconds, P = 0.005), and hard solid foods (114.1 vs 76.4 seconds, P = 0.034) when compared with healthy controls. Subgroup analysis based on disease status showed no statistically significant differences in eating behaviors between active and inactive EoE. Total endoscopic reference score positively correlated with consumption time (r = 0.53, P = 0.008) and number of chews (r = 0.45, P = 0.027) for chewable foods and with number of chews (r = 0.44, P = 0.043) for hard solid foods. Increased consumption time correlated with increased eosinophil count (r = 0.42, P = 0.050) and decreased esophageal distensibility (r = -0.82, P < 0.0001). DISCUSSION: Altered eating behaviors including increased chewing and increased consumption time can be seen in pediatric patients with EoE, can persist despite histologic remission, and may be driven by changes in esophageal distensibility. [ABSTRACT FROM AUTHOR]

The term "feeding difficulties" refers to a spectrum of phenotypes characterized by suboptimal intake of food and/or lack of age‐appropriate eating habits. While it is evident that feeding difficulties are prevalent within healthy children, no consensus has been reached for those with food allergies. The aim of this study was to systematically review all the available literature reporting the prevalence of feeding difficulties within food allergic children. We searched eight international electronic databases for all published studies until June 2022. International experts in the field were also contacted for unpublished and ongoing studies. All publications were screened against pre‐defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta‐analyses, so narrative synthesis of quantitative data was performed. A total of 2059 abstracts were assessed, out of which 21 underwent full‐text screening and 10 studies met the study criteria. In these, 12 different terms to define feeding difficulties and 11 diagnostic tools were used. Five papers included data of feeding difficulty prevalence in children with food allergies, ranging from 13.6% to 40%. Higher prevalence was associated with multiple food allergies. The current literature suggests that feeding difficulties are prevalent within food allergic children, particularly those with multiple food allergies. However, the heterogeneity of terminologies and diagnostic tools makes drawing conclusions challenging. Consensus guidelines for the diagnosis and management of feeding difficulties within food allergic children and further research on the development and perpetuation of feeding difficulties are needed to appropriately manage such patients. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disorder, linked with sensitization to food and airborne allergens. Dietary manipulations are proposed for the management of EoE inflammation and are often successful, confirming the etiological role of food allergens. Three different dietary approaches are widely used: the elemental, the empirical, and the allergy-test-driven approach. We performed a systematic review to assess the evidence on the association of allergens, detected by allergy tests, with clinically confirmed triggers of EoE. We systematically searched PubMed, Scopus, Embase, and the Cochrane Library, through 1 June 2021. We sought studies examining the correlation of skin-prick tests (SPT), atopy patch tests (APT), specific IgE, and serum-specific IgG4, with confirmed triggers of EoE. Data on the use of prick–prick tests were also extracted. Evidence was independently screened by two authors against predefined eligibility criteria. Risk of bias was assessed with the ROBINS-I tool. Of 52 potentially eligible studies, 16 studies fulfilling quality criteria were included. These studies used one to three different allergy tests detecting food sensitization. The positive predictive value was generally low to moderate but higher when a combination of tests was used than single-test evaluations. None of the selected studies used serum-specific IgG4. Although an extreme methodological variability was noticed in the studies, allergy-based elimination diets were estimated to be efficient in 66.7% of the cases. The efficacy of targeted elimination diets, guided by SPT, sIgE, and/or APT allergy tests, does not appear superior to empirical ones. In the future, tests using esophageal prick testing or ex vivo food antigen stimulation may prove more efficient to guide elimination diets. [ABSTRACT FROM AUTHOR]

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life‐threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross‐contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross‐contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms. EoE can occur at any age and has different clinical manifestations depending on the age onset. To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis. According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis. A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment. This review will provide a practical guide to assist pediatricians treating children with EoE. Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE. [ABSTRACT FROM AUTHOR]

Objective: There are no disease‐modifying therapies for the treatment of eosinophilic oesophagitis (EoE), which is driven by non‐IgE‐mediated allergic inflammation. A recent clinical trial of milk epicutaneous immunotherapy (EPIT) has shown initial promise, with 47% of treated EoE patients tolerating milk without recurrence of disease. Mechanisms of EPIT in EoE have not been studied in humans. Here, we identify transcriptional changes in the peripheral CD4+ T‐cell compartment during active EoE and following EPIT. Methods: RNA isolation, sequencing and integrative data analysis were performed on peripheral CD4+ T cells isolated from 15 of 20 patients enrolled in a clinical trial of EPIT for EoE. Gene expression changes in peripheral CD4+ T cells were examined during diet therapy and following trial of milk antigen EPIT. Results: We identify 244 differentially expressed genes in peripheral blood CD4+ cells of EoE patients consuming versus those eliminating milk, and 129 DEGs in CD4+ cells were isolated after EPIT versus after placebo (FDR ≤ 0.05). Gene set enrichment analysis identifies enrichment of hallmark interferon‐α and interferon‐γ response pathways in peripheral CD4+ T cells from EoE patients during active disease on a milk‐containing diet. We demonstrate overlap of this gene signature with the altered gene expression signature seen in EoE patient biopsy tissue. EPIT therapy response is associated with significant enrichment in pathways related to T‐cell receptor signalling (P = 1.16 × 10−14), antigen presentation and costimulation, and cytokine signalling (P = 1.11 × 10−16), as well as upregulation of genes associated with regulatory T‐cell function. Conclusions: EoE is associated with distinct global transcriptional changes in CD4+ T cells, one feature of which is an IFN response signature. Clinically favorable response to EPIT is likely multifactorial but is associated with a distinct transcriptional profile in peripheral CD4+ cells supporting the hypothesis that EPIT alters peripheral CD4+ responses in EoE patients. [ABSTRACT FROM AUTHOR]

Keywords: eosinophils; esophagitis; food allergy; milk food allergy; epicutaneous immunotherapy EN eosinophils esophagitis food allergy milk food allergy epicutaneous immunotherapy 1573 1576 4 05/17/21 20210501 NES 210501 Eosinophilic esophagitis (EoE) is an allergic disease of the esophagus without any curative therapy. After CM-induced EoE was confirmed, EPIT was applied daily for 9 months during a CM-free period, followed by CM-containing diet for 2 months. Eosinophils, esophagitis, food allergy, milk food allergy, epicutaneous immunotherapy. [Extracted from the article]

Food protein‐induced enterocolitis syndrome is still a mysterious disease, pathogenically poorly characterized, although the first FPIES case has been described in 1967. Mainly, food protein‐induced enterocolitis syndrome diagnosis is based on clinical history. The oral food challenge remains the gold standard to confirm the diagnosis, especially in particular situations. Although there are no diagnostic laboratory or imaging tests which are specific for diagnosis, they could, however, sometimes be helpful to rule out clinical conditions which are similar to food protein‐induced enterocolitis syndrome reactions. The purpose of this review is to define the clinical features of FPIES and to summarize the current available tools for the diagnosis of FPIES. This review is intended to be a practical guide for the clinician facing a patient with food protein‐induced enterocolitis syndrome avoiding delayed diagnosis with unnecessary laboratory tests and detrimental treatments. Moreover, it highlights the unmet needs in diagnosis that require urgent attention from the scientific community to improve the management of patients with FPIES. [ABSTRACT FROM AUTHOR]

Background An increasing number of infants are diagnosed with food protein-induced enterocolitis syndrome ( FPIES), a non-IgE-mediated food allergy. Until now, T-cell, food-specific mechanisms have been hypothesized. Methods Sixteen children (11M, 5F), affected by FPIES from cow's milk, wheat, fruit, rice, and others, experienced 25 acute episodes managed at our emergency department ( ED) and eight FPIES reactions during oral food challenges ( OFC). We compared the laboratory data in resting conditions, in the absence of infectious diseases, with data collected during the 25 acute ED episodes (blood samples drawn at 2-12 hours) and the eight positive OFCs (three samples at 2, 6, and 12 hours). The onset of symptoms was used as a reference time point. Results In basal conditions, total IgE, WBC, neutrophil and eosinophil count, CRP, and SGPT were found normal. LDH and SGOT values were high (627.81±97.88 and 45.75±10.26 UI/L, respectively). During ED reactions, LDH and SGOT increased to 794.21±247.28 ( P=.028) and 51.08±16.99 UI/L ( P=.14) and neutrophils count and CRP to 8.44±3.82×103/μL ( P=.0009) and 3.27±5.73 mg/dL ( P=.0014), respectively. During positive OFC, LDH and SGOT did not vary significantly; CRP increased from 0.14±0.18 to 2.49±3.65 mg/dL ( P=.00189) and neutrophil count from 2.79±1.42 to 7.10±3.98×103/μL ( P=.00096). Conclusions FPIES reactions are characterized by neutrophilia and by a time-dependent, significant increase in CRP, indicating that inflammatory mechanisms are in place. This suggests new directions for research on FPIES pathogenesis. [ABSTRACT FROM AUTHOR]

Summary: Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. [Copyright &y& Elsevier]

CD4+ T-helper type 2 (TH2) cells, characterized by their expression of interleukin (IL)-4, IL-5, IL-9 and IL-13, are required for immunity to helminth parasites and promote the pathological inflammation associated with asthma and allergic diseases. Polymorphisms in the gene encoding the cytokine thymic stromal lymphopoietin (TSLP) are associated with the development of multiple allergic disorders in humans, indicating that TSLP is a critical regulator of TH2 cytokine-associated inflammatory diseases. In support of genetic analyses, exaggerated TSLP production is associated with asthma, atopic dermatitis and food allergies in patients, and studies in murine systems demonstrated that TSLP promotes TH2 cytokine-mediated immunity and inflammation. However, the mechanisms through which TSLP induces TH2 cytokine responses remain poorly defined. Here we demonstrate that TSLP promotes systemic basophilia, that disruption of TSLP-TSLPR interactions results in defective basophil responses, and that TSLPR-sufficient basophils can restore TH2-cell-dependent immunity in vivo. TSLP acted directly on bone-marrow-resident progenitors to promote basophil responses selectively. Critically, TSLP could elicit basophil responses in both IL-3-IL-3R-sufficient and -deficient environments, and genome-wide transcriptional profiling and functional analyses identified heterogeneity between TSLP-elicited versus IL-3-elicited basophils. Furthermore, activated human basophils expressed TSLPR, and basophils isolated from eosinophilic oesophagitis patients were distinct from classical basophils. Collectively, these studies identify previously unrecognized heterogeneity within the basophil cell lineage and indicate that expression of TSLP may influence susceptibility to multiple allergic diseases by regulating basophil haematopoiesis and eliciting a population of functionally distinct basophils that promote TH2 cytokine-mediated inflammation. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the accumulation of eosinophils in the esophagus. We report association of EoE with variants at chromosome 5q22 encompassing TSLP and WDR36 (rs3806932, combined P = 3.19 × 10−9). TSLP is overexpressed in esophageal biopsies from individuals with EoE compared with unaffected individuals, whereas WDR36 expression is unaltered between the two groups. These data implicate the 5q22 locus in the pathogenesis of EoE and identify TSLP as the most likely candidate gene in the region. [ABSTRACT FROM AUTHOR]

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient's needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies established a link between pattern recognition receptor-expressing HSCs, EMH and innate immune responses to bacterial or viral pathogens. However, the factors that regulate EMH and whether EMH is a conserved mechanism of innate immunity to diverse stimuli remain poorly defined. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of Lineage−, CD34+, c-Kit+ granulocyte-monocyte progenitor (GMP)-like cells in the periphery. TSLP-elicited progenitors possess the capacity to differentiate into macrophages, mast cells and basophils. Critically, adoptive transfer of TSLP-elicited GMP-like cells was sufficient to promote Th2 cytokine-dependent immunity to an intestinal helminth parasite, demonstrating a role for TSLP-elicited GMP-like cells in promoting inflammation. Further, circulating progenitor cells were also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting that the TSLP-EMH pathway may be operational in human disease. These data demonstrate a previously unrecognized role for TSLP in promoting EMH that contributes to the development of Th2-cytokine-mediated inflammation and identify the TSLP-EMH pathway as a possible therapeutic target to treat allergic inflammation. [ABSTRACT FROM AUTHOR]