TABLE 1.
Evidence for immune activation in functional dyspepsia at the cellular level.
| Findings | Associations | Methods | Population | Study details |
| Duodenal mucosal immune activation | ||||
| Eosinophil infiltration and degranulation | H&E, EM | 20 pediatric FD (Rome II), uncontrolled | United States, 2002 (Friesen et al., 2002) | |
| ↑ Epithelial CD8+ CD3+ cell infiltration | Flow cytometry | 6 H. pylori+ FD (Rome II) vs. 12 HC | France, 2007 (Gargala et al., 2007) | |
| ↑ Eosinophil infiltration | ∼ early satiety | H&E | 51 NUD (Rome II) vs. 48 HC | Sweden, 2007 (Talley et al., 2007) |
| ↑ Eosinophil infiltration | H&E | 51 NUD (Rome II) vs. 48 HC | Sweden, 2009 (Walker et al., 2009) | |
| ↑ Presence of CD8+ T cell aggregates | ∼ gastric emptying | IHC | 12 presumed pi FD vs. 12 unspecified FD | Belgium, 2009 (Kindt et al., 2009a) |
| ↑ CD68+ cells | ||||
| ↑ Histological duodenitis | ∼ epigastric burning | H&E, IHC, IF | 35 presumed pi FD (Rome III) vs. 20 HC | Japan, 2010 (Futagami et al., 2010) |
| ↑ Eosinophil, CD68+ cell and CCR2+ macrophage infiltration | ||||
| ↑ Eosinophil infiltration | ∼ allergy | H&E | 19 PDS (Rome III) vs. 89 HC | United Kingdom, 2010 (Walker et al., 2010) |
| ↑ Eosinophil and mast cell infiltration | ∼ TJ gene expression | IHC | 15 FD (Rome III) vs. 15 HC | Belgium, 2014 (Vanheel et al., 2014) |
| ↑ Eosinophil infiltration | ∼ PDS symptoms & abdominal pain | H&E | 33 FD (Rome II) vs. 22 HC | Australia, 2014 (Walker et al., 2014) |
| ↑ Eosinophil and mast cell infiltration | ∼ neuronal responses & PDS symptoms | IF (submucosa) | 18 FD (Rome III) vs. 20 HC | Belgium, 2015 (Cirillo et al., 2015) |
| ↑ Eosinophil and mast cell infiltration and degranulation | H&E, IHC, TB | 141 FD (Rome III) vs. 39 HC | China, 2015 (Wang et al., 2015) | |
| ↑ Mast cell infiltration and degranulation | TB | 48 FD (Rome III) vs. 21 HC | China, 2015 (Yuan et al., 2015a, b) | |
| ↑ Eosinophil degranulation | IHC | 96 FD (Rome III) vs. 24 HC | China, 2016 (Du et al., 2016) | |
| ↑ Eosinophil infiltration | IF | 9 FD (Rome III) vs. 5 HC | Japan, 2016 (Tanaka et al., 2016) | |
| ↑ Eosinophil infiltration | ∼ weight loss | H&E | 36 pediatric FD (Rome III) vs. 36 HC | Australia, 2017 (Wauters et al., 2017) |
| ↑ Eosinophil and mast cell infiltration, eosinophil degranulation | IHC, EM | 24 FD (Rome III) vs. 37 HC | Belgium, 2018 (Vanheel et al., 2018) | |
| ↑ Eosinophil infiltration and degranulation | ∼ presence of fine nerve fibers | H&E, EM | 51 FD (Rome III) vs. 35 HC | South Korea, 2019 (Lee et al., 2019) |
| ↑ Eosinophil and mast cell infiltration | IHC | 35 FD (Rome III) vs. 31 HC | Japan, 2019 (Taki et al., 2019) | |
| Eosinophil degranulation | ∼ FD symptoms | H&E | 178 FD (Rome II) vs. 249 HC | United States, 2020 (Järbrink-Sehgal et al., 2020) |
| ↑ Eosinophil infiltration | ∼ FD & PDS symptoms | H&E | 42 FD (Rome III) vs. 42 HC | Bangladesh, 2020 (Sarkar et al., 2020) |
| ↑ Mast cell infiltration | ∼ GI symptoms | IF (submucosa) | 13 FD (Rome III) vs. 24 HC | Italy/Belgium, 2020 (Giancola et al., 2020) |
| ↑ Eosinophil and mast cell infiltration | ∼ FD symptoms | H&E, IHC | 28 FD (Rome IV) vs. 30 HC | Belgium, 2021 (Wauters et al., 2021a) |
| Gastric mucosal immune activation | ||||
| ↑ Histological gastritis | H&E | 35 presumed pi FD (Rome III) vs. 20 HC | Japan, 2010 (Futagami et al., 2010) | |
| ↑ EC infiltration, mast cell and EC activation | IHC | 30 presumed pi FD (Rome III) vs. 20 HC | China, 2010 (Li et al., 2010) | |
| ↓ CD206+ macrophage and ICC abundance | IHC (myenteric plexus) | 9 FD (Rome III) vs. 9 HC | United States, 2021 (Pasricha et al., 2021) | |
| Systemic immune activation | ||||
| ↑ CD3+ CD45RO+ CD45RA+ cells | Flow cytometry | 23 FD (Rome II) vs. 32 HC | Belgium, 2009 (Kindt et al., 2009b) | |
| ↑ CD4+ α4β7+ CCR9+ cells | ∼ GI symptoms & gastric emptying | Flow cytometry | 45 FD (Rome II) vs. 35 HC | Australia, 2011 (Liebregts et al., 2011) |
H&E: hematoxylin & eosin, EM: electron microscopy, FD: functional dyspepsia, NUD: non-ulcer dyspepsia, HC: healthy control, IHC: immunohistochemistry, pi: post-infectious, IF: immunofluorescence, PDS: postprandial distress syndrome, TJ: tight junction, TB: toluidine blue, GI: gastrointestinal, EC: enterochromaffin cells, ICC: interstitial cell of Cajal.