Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia.
OBJECTIVE
Recent studies have shown that postinfectious functional dyspepsia (FD) symptoms may persist after elimination of gastrointestinal (GI) infection as well as postinfectious irritable bowel syndrome accompanying colonic inflammation. However, it is unclear whether intestinal chronic inflammation can contribute to clinical symptoms of certain FD patients such as postinfectious FD. To determine the relationship between local inflammation of the duodenum and clinical symptoms, we evaluated the infiltration of several phenotypes of duodenal inflammatory cells as well as gastric motility using (13)C urea breath test in postinfectious FD patients.


METHODS
We enrolled 136 consecutive patients diagnosed with FD according to Rome III criteria, and 20 healthy controls, after upper GI endoscopy. Gastric motility was evaluated by gastric emptying time (T-max) using the (13)C-acetate breath test. Upper abdominal symptoms including epigastric pain, epigastric burning, postprandial fullness, abdominal distension, and early satiety were assessed by questionnaire scores. We obtained biopsy specimens from the stomach and duodenum during upper GI endoscopy. Histological gastritis and duodenitis were assessed as mild, moderate, or severe according to previously described criteria. Characteristics of inflammatory cells and neuroendocrine cells were determined immunohistochemically with antibodies to CD3, CD68, CCR2, Vdelta1 TCR, and serotonin.


RESULTS
Endoscopic duodenitis was observed in only 5.7% of postinfectious FD patients. However, the rates of histological duodenitis in duodenal biopsies of postinfectious FD patients were 17% for mild, 26% for moderate, and 57% for severe grades of duodenitis. The degree of histological duodenitis of postinfectious FD patients was significantly greater than that of healthy volunteers. There was a significant correlation between epigastric burning and the degree of duodenitis in postinfectious FD patients. There was no significant difference in histological duodenitis and T-max value in the postinfectious FD patients with or without Helicobacter pylori infection. In addition, CD68-positive cell number in postinfectious FD patients was significantly increased compared with the numbers in subjects with epigastric pain syndrome or postprandial distress syndrome and in healthy volunteers. CCR2-/CD68-double positive cell number in postinfectious FD patients was significantly (P=0.009) increased compared with those in healthy volunteers.


CONCLUSIONS
Migration of inflammatory cells, in particular, duodenal CCR2-positive macrophages, may have an important function in the pathophysiology of postinfectious FD patients.
Futagami
Seiji
S
Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan. seiji-f@nms.ac.jp
Shindo
Tomotaka
T
Kawagoe
Tetsuro
T
Horie
Akane
A
Shimpuku
Mayumi
M
Gudis
Katya
K
Iwakiri
Katsuhiko
K
Itoh
Takashi
T
Sakamoto
Choitsu
C
D000704:Analysis of Variance; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001706:Biopsy; D016022:Case-Control Studies; D002465:Cell Movement; D004378:Duodenal Diseases / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D004415:Dyspepsia / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D016099:Endoscopy, Gastrointestinal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005746:Gastric Emptying; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008297:Male; D054390:Receptors, CCR2 / Q000276:immunology*; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054390:Receptors, CCR2; C515334:CCR2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule