scholarly journals Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions

2020 ◽  
Vol 11 ◽  
Author(s):  
Alfred D. Doyle ◽  
Mia Y. Masuda ◽  
Hirohito Kita ◽  
Benjamin L. Wright
Keyword(s):  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Disease Onset ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Mucus Production ◽  
Local Immunity ◽  
Esophageal Eosinophilia ◽  
Type 2 Inflammation

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.

scholarly journals Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

2022 ◽  
Vol 12 ◽  
Author(s):  
Francesca Racca ◽  
Gaia Pellegatta ◽  
Giuseppe Cataldo ◽  
Edoardo Vespa ◽  
Elisa Carlani ◽  
...  
Keyword(s):  
Eosinophilic Esophagitis ◽  
Therapeutic Targets ◽  
Deep Understanding ◽  
Surface Proteins ◽  
Barrier Dysfunction ◽  
Intrinsic Factors ◽  
First Line Therapy ◽  
Epithelial Barrier Dysfunction ◽  
Type 2 Inflammation

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.

scholarly journals The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

2019 ◽  
Vol 11 (480) ◽  
pp. eaav2685 ◽  
Author(s):  
Donald Y. M. Leung ◽  
Agustin Calatroni ◽  
Livia S. Zaramela ◽  
Petra K. LeBeau ◽  
Nathan Dyjack ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Sampling Method ◽  
Skin Barrier ◽  
Skin Surface ◽  
Transepidermal Water Loss ◽  
Barrier Dysfunction ◽  
Ceramide Content ◽  
Immune Pathways

Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD FA+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA−) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA+ were substantially lower than in AD FA− and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD FA+ had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA+. The skin transcriptome of AD FA+ had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD FA+, whereas filaggrin breakdown products were negatively correlated with AD FA+. These data suggest that the most superficial compartment of nonlesional skin in AD FA+ has unique properties associated with an immature skin barrier and type 2 immune activation.

scholarly journals Chemicals in moisturizers may promote type 2 inflammation and food allergy

2021 ◽  
Author(s):  
Iben Frier Ruge ◽  
Ian Kimber ◽  
Louise Cunningham ◽  
John Paul McFadden ◽  
Jacob P. Thyssen
Keyword(s):  
Food Allergy ◽  
Type 2 Inflammation

scholarly journals Cross-sectional imaging of intestinal barrier dysfunction by confocal laser endomicroscopy can identify patients with food allergy in vivo with high sensitivity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timo Rath ◽  
Walburga Dieterich ◽  
Christiane Kätscher-Murad ◽  
Markus F. Neurath ◽  
Yurdagül Zopf
Keyword(s):  
Food Allergy ◽  
Intestinal Barrier ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

AbstractFood allergy (FA) affects approximately 3 to 4% of the adult population in westernized countries. Suspected FA is even more prevalent and requires extensive diagnostic work-up. Within this study, we evaluated whether assessment of the integrity of the epithelial barrier by confocal laser endomicroscopy (CLE) during colonoscopy can be used as a screening tool to identify patients with FA. 60 patients with suspected FA were prospectively included. Serology with total and food-specific IgE, anti-tissue transglutaminase, skin prick testing, food intolerance tests, food intake registration and assessment of clinical complaints were performed. During colonocopy, standardized CLE was performed in the terminal ileum and at two colorectal sites. Analysis of CLE images included functional (i.e. presence of epithelial barrier dysfunction) and quantitative parameters of intestinal architecture. 27 of 60 patients (45%) were diagnosed with FA. Barrier dysfunction was analyzed on 65.837 ileal and on 93.251 colonic images. 96% of patients with FA exhibited functional and structural barrier defects while barrier dysfunction was found in only 33% of patients without FA (p < 0.0001). Visualizing barrier dysfunction with CLE for in vivo diagnosis of FA had a sensitivity and specificity of 96% and 67%, respectively, with a positive and negative prediction of 70% and 96%, respectively. Parameters intrinsic to the crypt architecture including crypt diameter, intercrypt distance, crypt lumen diameter and colonic vasculature were not different between patients with and without FA. CLE-based imaging of the intestinal barrier during colonoscopy might help in stratifying patients with suspected FA for further diagnostic work-up.

scholarly journals Current Insights into Atopic March

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1067
Author(s):  
Mitsuru Tsuge ◽  
Masanori Ikeda ◽  
Naomi Matsumoto ◽  
Takashi Yorifuji ◽  
Hirokazu Tsukahara
Keyword(s):  
Oxidative Stress ◽  
Environmental Pollutants ◽  
Skin Barrier ◽  
Allergic Diseases ◽  
Barrier Dysfunction ◽  
Atopic March ◽  
Inflammatory Conditions ◽  
And Oxidative Stress ◽  
Type 2 Inflammation

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

scholarly journals Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1165
Author(s):  
Michele Ghezzi ◽  
Elena Pozzi ◽  
Luisa Abbattista ◽  
Luisa Lonoce ◽  
Gian Vincenzo Zuccotti ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Treatment Strategies ◽  
Allergic Diseases ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
New Treatment ◽  
Epithelial Barrier Dysfunction ◽  
And Function ◽  
Innate Defence

Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.

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