Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation

Abstract

We recently identified mucosal mast cell and eosinophil hyperplasia in association with a duodenal impaired barrier function in functional dyspepsia (FD). We aimed to further describe the implication of these immune cells by assessing their activation state at the ultrastructural level and by evaluating the association between impaired epithelial integrity and immune activation. Duodenal biopsies were obtained from 24 FD patients and 37 healthy controls. The ultrastructure of mast cells and eosinophils was analyzed by transmission electron microscopy. Transepithelial electrical resistance and paracellular permeability were measured to evaluate epithelial barrier function. The type of degranulation in eosinophils and mast cells was piecemeal. Eosinophils displayed higher degree of degranulation in FD patients than in controls (p < 0.0001). Quantification revealed a decreased granular density in eosinophils of FD patients (p < 0.0001). The degree of degranulation in mast cells was similar in both groups. However, a more heterogeneous profile was found in the FD group (p < 0.0001). No association between epithelial integrity and the number and activation state of mucosal eosinophils and mast cells was found. We demonstrated ultrastructural changes in degranulation state of eosinophils and mast cells, suggesting that eosinophil and mast cell activation play a role in the pathophysiology of FD.

Duodenal low‐grade inflammation and expression of tight junction proteins in functional dyspepsia

“…However, the staining of claudin‐1 was not on the apical side of duodenal epithelia in this study. A recent report by Vanheel presented no association between epithelial integrity and the number of mucosal eosinophils and mast cells . The present study found increased claudin‐3 mRNA expression in patients with FD.…”

Micro‐inflammation in functional dyspepsia: A systematic review and meta‐analysis

“…Of the 10 studies that evaluated mast cell counts, 5 studies reported increased mast cell infiltration in the duodenum and 1 in the duodenal bulb. The pooled results showed increased duodenal mast cell counts (SMD = 0.66, 95%CI 0.20‐1.13, P = .005) in individuals with FD . There was heterogeneity observed among the studies ( I 2 = 82%, P < .001) but no publication bias was detected (Egger's test P = .833).…”

“…Nineteen studies examined eosinophil infiltration in FD. A pooled evaluation showed increased duodenal eosinophils in individuals with FD (SMD = 0.95, 95%CI 0.66‐1.24, P < .001) compared to controls (Figure A) . Although significant heterogeneity ( I 2 = 88%, P < .001) and publication bias (Egger's test P = .004, Figure B) were observed, no single publication was found to bias the results in the sensitivity analysis (Figure C).…”

“…A pooled evaluation showed increased duodenal eosinophils in individuals with FD (SMD = 0.95, 95%CI 0.66-1.24, P < .001) compared to controls ( Figure 3A). [5][6][7]15,17,[19][20][21][24][25][26][27][28][29][30][31][32][33][34] Although significant heterogeneity (I 2 = 88%, P < .001) and publication bias (Egger's test P = .004, Figure 3B) were observed, no single publication was found to bias the results in the sensitivity analysis ( Figure 3C Figure 4A, B), while no difference in duodenal eosinophil counts was observed between EPS and PDS subgroups ( Figure 4C). We also found that eosinophil counts were increased in both the first (SMD = 0.74, 95%CI 0.41-1.08, P < .0001) and second (SMD = 0.86, 95%CI 0.68-1.04, P < .00001) portions of the duodenum among individuals with FD compared to controls ( Figure 5A, B).…”

“…The pooled results showed increased duodenal mast cell counts (SMD = 0.66, 95%CI 0.20-1.13, P = .005) in individuals with FD. 7,10,[27][28][29][32][33][34][35][36] There was heterogeneity observed among the studies (I 2 = 82%, P < .001) but no publication bias was detected (Egger's test P = .833).…”