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27/04/2018

VHIR researchers study the role of eosinophils and mast cells in functional dyspepsia

dispepsia_funcional_884

27/04/2018

The mucosa of the duodenum of patients with functional dyspepsia contains a higher number of eosinophils and mast cells and that both cell types have a high degree of activation.

A joint study carried out by research group in http://en.vhir.org/portal1/grup-equip.asp?s=recerca&contentid=187018 Physiology and Pathophysiology of the Digestive Tract of VHIR together with the Centre for Translational Research on Gastrointestinal Disorders (https://www.nature.com/articles/s41598-018-23620-y" TARGID) of Leuven, Belgium has demonstrated that the mucosa of the duodenum of patients with functional dyspepsia contains a higher number of eosinophils and mast cells and that both cell types have a high degree of activation. The study was recently published in the journal https://www.nature.com/articles/s41598-018-23620-y" Scientific Reports.There is a growing number of studies reporting a low degree of duodenal inflammation in patients with functional dyspepsia and based mainly on the histological detection of a slight but significant increase in the number of mucosal immune cells, mainly eosinophils and mast cells. However, until now, the activation status of these cells has not been analysed.At VHIR, Dr. María Vicario's team was in charge of evaluating the number and activation of mast cells and eosinophils using optical and electron microscopy techniques in patients with functional dyspepsia. This group is specialized in the morphological analysis of intestinal tissue and in the quantification of the degree of cellular activation according to its ultra-structure. For its part, the Leuven group, led by Dr. Ricard Farré, recruited participants (patients with functional dyspepsia and healthy volunteers) and performed functional studies on duodenal biopsies to assess "intestinal barrier function."In a previous study, "we showed an increase in duodenal permeability with a greater infiltration of mast cells and eosinophils in patients with functional dyspepsia and we identified an association between proteins that constitute the epithelial barrier and low-grade inflammation," recalls Dr. María Vicario, head of the Mucosal Translational Immunology Laboratory of the Group of http://en.vhir.org/portal1/grup-equip.asp?s=recerca&contentid=187018 Physiology and Pathophysiology of the Digestive Tract of VHIR.Now, the present study has shown a higher degree of activation of eosinophils and mast cells in patients with functional dyspepsia compared to healthy subjects. These cells have a higher degranulation profile and heterogeneous granular morphology, indicating a greater release of mediators into the extracellular space and different content of their cytoplasmic granules, respectively."The analysis of the cellular ultrastructure has allowed us to identify greater degranulation in eosinophils and mast cells of patients compared to healthy ones, although we do not know which molecules synthesize, store and release these cells in a differential way," explains Dr. Vicario. Both cell types are involved in inflammatory and allergic diseases and are actively involved in the regulation of the intestinal barrier. The study suggests, however, that the participation of these cells in the pathophysiology of functional dyspepsia is not associated with an inflammatory response, since no differences have been detected in the expression of specific molecules of each of these cells with pro-inflammatory activity.Likewise, for the first time, a heterogeneous and complex granular morphology has been identified in the mast cells of these patients, which suggests the synthesis of alternative mediators that could be responsible for the functional changes detected in this group. "This study shows the versatility of resident cells of the duodenal mucosa, whose mediators may be responsible for the characteristic digestive alterations in these patients" -points out Dr. Vicario-"so that deepening its characterization can provide us with new therapeutic targets." Functional dyspepsiaDyspepsia is a heterogeneous functional disorder of unknown origin and very common in developed countries, affecting up to 30% of the general population. It is defined as a group of symptoms that originate in the upper gastrointestinal tract (stomach and upper small intestine) in the absence of structural or organic cause or metabolic disease that explains the symptoms. Symptoms include pain or discomfort in the upper abdomen as well as symptoms of burning, pressure or fullness. Current research is focused on identifying their physiopathology and the search for effective treatments in order to improve the quality of life of patients and reduce the high healthcare costs generated by this disorder.

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