Mucosal inflammation, esophageal eosinophilia and celiac disease; A little “pinch” will have to do you

When a mucosal surface is injured, inflammatory responses ensue. These responses are characterized by the well-orchestrated accumulation of reparative leukocytes that protect and heal the mucosa during a process that often goes unrecognized. Under other circumstances, genetically predisposed hosts encounter exogenous or endogenous triggers that lead to pathological inflammation, tissue damage, and organ dysfunction. The gastrointestinal tract is the target site for this process in a number of diseases, including inflammatory bowel diseases, celiac disease, and eosinophilic esophagitis (EoE)..

Eosinophilic Esophagitis - Pathophysiology and its Clinical Implications

Eosinophilic Esophagitis is an antigen mediated chronic disease that is distinct from gastroesophageal reflux disease. EoE an emerging clinical problem that is rapidly growing in incidence and in recognition. It is characterized clinically by feeding dysfunction, dysphagia and reflux-like symptoms. Histologically EoE is identifiable by a dense epithelial eosinophilic infiltrate. Experimental modeling and clinical studies over the last decade have greatly improved our understanding of this disease and led to improvements in clinical understanding and the assessment of therapeutic options for patients and their clinicians who manage this disease. In this review we review the cliniopathologic diagnostic criteria and our understanding of EoE as an allergic disease with genetic and immunological components in the pathophysiology. We make note of the berth of studies defining the importance of the epithelial barrier and discuss the concept of barrier function as an initiating or perpetuating factor for this disease. The relationship between the symptoms of dysphagia, feeding dysfunction and our current knowledge of the underlying pathophysiologic mechanisms of these clinical indicators, as well as advances in clinical assessment of decreased esophageal distensibility and narrowing in EoE patients. Lastly, therapeutic implications relating to the advances that have led to our current understanding of the pathophysiology of EoE are explored

Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies

Eosinophils are implicated in the pathophysiology of a spectrum of eosinophil-associated diseases, including gastrointestinal eosinophilic diseases (EGIDs). Biologics that target the IL-5 pathway and are intended to ablate eosinophils have proved beneficial in severe eosinophilic asthma and may offer promise in treating some endotypes of EGIDs. However, destructive effector functions of eosinophils are only one side of the coin; eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggest tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) pressures, which may differentially impact disease outcomes. This may be particularly relevant to the GI tract, wherein the highest density of eosinophils reside in the steady state, resident immune cells are exposed to an especially broad range of external and internal environmental pressures, and greater eosinophil longevity may uniquely enrich for co-expression of eosinophil sub-phenotypes. Here we review the growing evidence for functional sub-phenotypes of intestinal tissue eosinophils, with emphasis on the multifactorial pressures that shape and diversify eosinophil identity and potential targets to inform next-generation eosinophil-targeting strategies designed to restrain inflammatory eosinophil functions while sustaining homeostatic roles

Ultrastructural features of eosinophilic oesophagitis: impact of treatment on desmosomes

Aims—A growing body of evidence suggests a role for altered epithelial barrier function in the pathophysiology of eosinophilic oesophagitis (EoE), but few have described the epithelial structure during inflammation. The purpose of this study was to define ultrastructural features of active, inactive EoE and control subject’s oesophageal epithelia. Methods—We prospectively enrolled patients undergoing diagnostic upper endoscopy for evaluation of EoE. Mucosal pinch biopsies were obtained from the distal oesophagus and processed for routine histology and electron microscopic assessment. Clinical features of enrolled subjects were analysed and subjects were divided into four groups: normal, gastroesophageal reflux disease (GERD), inactive EoE and active EoE. Representative photomicrographs of the basal and superficial epithelia were reviewed for abnormalities. Desmosomes were quantified on the surface of epithelia three to four prickle-cell layers above the basal layer. Results—Twenty-nine paediatric cases (ages 2–18 years) were enrolled in the study. We observed a significant decrease in the number of desmosomes per cell (DPC) of subjects with active EoE compared with inactive EoE, GERD and normal epithelia. With respect to DPC, no significant differences were found between inactive EoE compared with GERD or normal subjects. Additional ultrastructural features observed included epithelial microplicae and evidence of eosinophil transmigration, degranulation, and sombrero formation. Conclusions—Consistent with clinical and molecular findings, our ultrastructural data provide support for an altered oesophageal barrier in paediatric cases with active EoE, which may improve following treatmen