Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome.
BACKGROUND
Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen Chlamydia could be involved in the pathogenesis of IBS.


METHODS
We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively.


RESULTS
Chlamydia LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for C. trachomatis major outer membrane protein (MOMP). Staining for C. pneumoniae was negative in both patients and controls. Chlamydia LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS.


CONCLUSIONS
We found C. trachomatis antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.
Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Aldona
A
Dlugosz
Hans
H
Törnblom
Ghazaleh
G
Mohammadian
Gareth
G
Morgan
Béla
B
Veress
Benjamin
B
Edvinsson
Gunnar
G
Sandström
Greger
G
Lindberg
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis*; D001706:Biopsy; D015153:Blotting, Western; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity; D019858:Enteroendocrine Cells / Q000276:immunology* / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000382:microbiology*; D007583:Jejunum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000942:Antigens, Bacterial