26 research outputs found
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