Nerve fiber overgrowth in patients with symptomatic diverticular disease.

BACKGROUND: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. METHODS: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers). KEY RESULTS: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. CONCLUSIONS AND INFERENCES: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.

Pathophysiology of diverticular disease.

INTRODUCTION: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

Tumour necrosis factor-alpha expression in segmental colitis associated with diverticulosis down-regulates after treatment.

BACKGROUND AND AIMS: Tumour necrosis factor-α (TNF-α) expression may be increased in segmental colitis associated with diverticulosis (SCAD). Our aim was to assess TNF-α expression in SCAD in relationship to the treatment. METHODS: 10 patients affected by severe (type B and D) SCAD were studied (6 males, 4 females, mean age 60.54 years, range 43-85 years). All patients were treated with beclomethasone dipropionate 10 mg/day plus a probiotic preparation VSL#3 for 8 weeks. At that time, clinical, endoscopic and histological reassessment was performed. Controls were 5 patients with active ulcerative colitis (UC). RESULTS: After treatment, all SCAD B and no SCAD D patients were in remission. The TNF-α expression dropped from 42.7% (+/-7.58) to 15.7% (+/-2.6) in SCAD B patients (p=0.001), and from 40% (+/-5.9) to 28.6% (+/-5.3) in SCAD D patients (p=0.005). In UC patients, the TNF-α expression dropped from 45.5% (+/-5.09) to 22.5% (+/-2.5) (p=0.001). Neither SCAD B nor SCAD D patients showed a significant difference in TNF-α expression compared to UC after treatment. Finally, TNF-α was significantly overexpressed in SCAD D than in SCAD B at the end of treatment (p=0.048). CONCLUSIONS: TNF-α expression in SCAD down regulates after treatment, and seems to be related to the clinical response to therapy. This behaviour, similar to that of Inflammatory Bowel Diseases (IBD), confirms that this disease should be considered as a subtype of IBD.

[The role of immune system in development of structural changes in colonic mucosa in diverticulosis].

AIM: To determine the role of immune response with production of auto- and heterologous antibodies (Ab) in development of the pathological process and in structural changes in colon mucosa (CM) in diverticulosis (Dv). MATERIAL AND METHODS: Of 219 Dv patients, 39 were newly diagnosed with x-ray-detected signs of previous inflammation (group 1), 180 had earlier detected Dv which was confirmed and endoscopic examination detected inflammation (group 2). The comparison group consisted of 25 patients with irritable colon syndrome. The immune status was assessed by concentration of immunoglobulins (Ig), auto- and heterologous Ab. Antibodies to catalytic cytoplasmic antigens to proteinase-3, myeloperoxidase, bactericide protein BPI, tissue transglutaminase (tTG) and antiglycanic Ab were detected with solid-phase enzyme immunoassay. RESULTS: IgA and IgG levels in group 2 were significantly higher than in group 1 and in the controls. Elevation of both IgA and IgG levels reflects activation of B-cell immunity. Group 2 patients had a higher level of Ab to endogenic peptides Saccharomyces cerevisiae (ASCA) of class IgG and IgA than group 1 and controls. The level of Ab to tissue molecules was elevated: antibodies to tTG IgG were detected in both groups--in group 2 twice more often than in group 1, while Ab to BPI--in 27% cases in group 1 and in 97%--in group 2. IgG Ab to antigens associated with phagocytic cells were detected in group 2, while Ab in group 1 were positive in single cases. CONCLUSION: Activation of immune response with a high concentration of IgA and IgG, Ab to tissue antigens (BPI, tTG) and IgGAb to catalytic antigens is characteristic of chronic course of Dv. Morphological changes in CM reflect different severity of inflammation-dystrophic process.