Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. METHODS: Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. RESULTS: We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). CONCLUSIONS: Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More Comparable with that of Patients with Crohn's Disease.

BACKGROUND: The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. METHODS: Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. RESULTS: A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. CONCLUSIONS: The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

Correlation between serum serotonin and endoscopy inflammation scores in patients with ileal pouches.

BACKGROUND: Inflammatory and functional complications are common in patients with inflammatory bowel disease (IBD) after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The pathogenesis of these complications remains poorly understood, and there is discrepancy between the clinical symptoms and objective endoscopic inflammation scores in these patients. While serum serotonin level has been reported to be associated with symptoms of irritable bowel syndrome, its association with ileal pouch disorders has not been studied. AIM: To investigate the association between serum serotonin level and symptoms and endoscopic inflammation in patients with IPAA. METHODS: A total of 185 consecutive eligible IPAA patients who presented to a specialized Pouchitis Clinic from Jan 2009 to May 2009 were prospectively recruited. Patients were divided into 4 groups: normal pouch, irritable pouch syndrome (IPS), inflammatory pouch disorders (Crohn's disease, acute and chronic pouchitis, and cuffitis), and surgical complications. Serum serotonin level was measured and analyzed for correlation with clinical and endoscopic inflammation scores. RESULTS: Demographic and clinical variables were evaluated, including age, gender, smoking history, duration of UC, duration of the pouch, and disease category of the pouch. The median fasting serum serotonin level was comparable among the 4 groups: 94.0 ng/ml (interquartile range [IQR], 70.0, 128.1), 89.2 ng/ml (IQR 54.2, 155.9), 90.3 ng/ml (IQR 49.7, 164.1), 77.9 ng/ml (IQR 54.7, 129.0), for normal pouch, irritable pouch, inflammatory pouch disorders, and surgical complication groups, respectively (p=0.91). A significant association between serum serotonin level and the Pouchitis Disease Activity Index (PDAI) endoscopy subscore of the pouch (odds ratio [OR]=1.9, 95% confidence interval [CI]: 1.2, 2.9, p<0.05) and total PDAI endoscopy score (OR=1.8; 95% CI: 1.2, 2.8, p<0.05) in the inflammatory complication group were noted. CONCLUSIONS: Serum serotonin level appears to correlate with the PDAI endoscopy subscores and total PDAI score in patients with inflammatory complications suggesting that the hormone may be involved in mechanisms of mucosal inflammation. These findings may promote future treatment strategies for patients with pouch inflammation.

Seroreactivity to E. coli outer membrane protein C antibodies in active inflammatory bowel disease; diagnostic value and correlation with phylogroup B2 E. coli infection.

BACKGROUND: Several serologic tests, including anti-outer membrane porin C antibody (Omp C), are used for screening and as marker of disease course in inflammatory bowel diseases (IBD). Our aim was to investigate possible differences in Omp C level in patients with active and inactive IBD compared to controls. METHODS: All blood samples were tested for Omp C. Disease activity was evaluated by Harvey Bradshaw Index, Simple Clinical Activity Index and Modified Pouchitis Disease Activity Index. RESULTS: Blood samples were collected from 113 patients and 60 controls. Patients with active IBD did not have a higher level of Omp C than patients in remission. Surprisingly, in patients with active Crohn's disease a significantly lower level of Omp C was found compared with patients with inactive Crohn's disease (p < 0.05). All other groups among patients with IBD did have a significantly higher level of Omp C, compared with controls, including patients with acute gastroenteritis (p < 0.05). Although IBD patients with phylogroup B2 E. coli cultured from their fecal samples, were more likely to have a positive Omp C test (p < 0.05), this could not explain the low Omp C level in the subgroup of patients with active Crohn's disease. CONCLUSIONS: Omp C titer was not raised in patients with active IBD compared with patients in remission. In addition, there was no difference in Omp C level in patients with active Crohn's disease compared with controls. These observations do not support the use of Omp C serology testing, either in disease activity assessment, or in screening for active Crohn's disease.

Clinical utility of C-reactive protein in patients with ileal pouch anal anastomosis.

BACKGROUND: Inflammatory and noninflammatory complications of ileal pouch-anal anastomosis (IPAA) are common after restorative proctocolectomy for ulcerative colitis (UC). The clinical utility of C-reactive protein (CRP) in ileal pouch disorders has not been investigated. MATERIALS AND METHODS: All IPAA patients with underlying UC who had serum CRP tested within 2 weeks of pouch endoscopy were included. The correlation between the level of serum CRP and the Pouch Disease Activity Index (PDAI) scores were evaluated. Diagnostic accuracy of CRP in assessing disease activity by PDAI endoscopy subscores was evaluated. RESULTS: There were 83 patients (with a total 88 CRP tests), including normal pouches (n = 7), active pouchitis (n = 6), chronic pouchitis (n = 18), Crohn's disease of the pouch (n = 23), cuffitis (n = 13), irritable pouch syndrome (n = 10), and surgery-associated complications (n = 11). Levels of CRP did not differ significantly among healthy and diseased pouch groups. CRP levels significantly correlated with the PDAI endoscopy subscores in the pouch body (P = 0.006) and afferent limb (P = 0.03). A CRP level of greater than 0.7 mg/dL for CRP using the receiver operating characteristics curve obtained the best sensitivity of 69.7% and specificity of 63.6% to detect active pouch inflammation. CONCLUSIONS: Serum CRP levels correlated with endoscopic inflammation in the pouch and afferent limb. Elevated CRP levels might be useful to monitor the degree of inflammatory activity in pouch noninvasively. However, the CRP level as a snapshot had a limited role in distinction between healthy and diseased pouch conditions diagnosed based on longitudinal clinical and endoscopic evaluation.

Serologic responses in indeterminate colitis patients before ileal pouch-anal anastomosis may determine those at risk for continuous pouch inflammation.

PURPOSE: Although acute pouchitis after ileal pouch-anal anastomosis is common and easily treated, continuous pouch inflammation seen clinically as chronic, antibiotic-dependent pouchitis, and/or Crohn's disease remains a difficult management problem. Compared with ulcerative colitis, indeterminate colitis patients undergoing ileal pouch-anal anastomosis have a higher incidence of continuous pouch inflammation, which may represent persistent immune reactivity to microbial antigens. Antibody responses to three microbial antigens (oligomannan anti-Saccharomyces cerevisiae, outer membrane porin C of Escherichia coli, and an antigen (I2) from Pseudomonas flourescens) are more commonly seen in Crohn's disease, whereas antibodies to a cross-reactive antigen (perinuclear antineutrophil cytoplasmic antibodies) is more suggestive of ulcerative colitis. We examined whether preoperative serologic responses to these antigens were associated with Crohn's disease in indeterminate colitis patients after ileal pouch-anal anastomosis. METHODS: Twenty-eight indeterminate colitis patients undergoing ileal pouch-anal anastomosis were prospectively assessed for the development of pouchitis or Crohn's disease. Serologic responses were determined by enzyme-linked immunosorbent assay and immunofluorescence. Patients were classified based on four predominant profiles of antibody expression. Antibody profiles were determined before knowledge of clinical outcome. RESULTS: Median follow-up was 38 (range, 3-75) months. Of 16 patients (61 percent) who developed pouch inflammation, 4 (25 percent) had acute pouchitis and 12 (75 percent) had continuous pouch inflammation (9 had chronic pouchitis, 3 had Crohn's disease). No preoperative clinical factor predicted the development of these pouch complications. Overall, 16 patients (57 percent) had a positive antibody reactivity profile. Serologic expression of any marker alone did not predict the development of continuous pouch inflammation. However, continuous pouch inflammation developed in 10 of 16 patients (63 percent) who had a positive antibody reactivity profile compared with only 2 of 12 patients (17 percent) who had a negative antibody reactivity profile (P = 0.015). CONCLUSIONS: Indeterminate colitis patients who have a positive antibody reactivity profile before ileal pouch-anal anastomosis have a significantly higher incidence of continuous pouch inflammation after surgery than those with a negative profile.

Altered expression of the lymphocyte activation markers CD30 and CD27 in patients with pouchitis.

BACKGROUND: The mechanism underlying the development of ileal pouch inflammation in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is unclear. Persistent systemic T cell activation or expansion of specific memory cell populations could predispose certain patients to develop local inflammation within the neo-rectum. Therefore, the aim was to study the expression of the lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30 levels and mucosal CD30 expression in patients with pouchitis and in controls. METHODS: Flow cytometry was performed on PBMC isolated from patients with pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26) and normal controls (n = 20) by ELISA. CD30 expression was quantified in pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage immunoperoxidase method. RESULTS: Naive CD45RO-CD27+ PBMC were significantly decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03). CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1-290) U/ml, P=0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the mucosa, the numbers of CD30+ cells were increased in pouchitis compared to non-inflamed pouches (P = 0.02). CONCLUSIONS: Increased sCD30 in pouchitis is associated with elevated mucosal expression. Of the activation markers studied, only the circulating naïve CD27+ population differed in pouchitis patients compared with controls. The observed decrease in this cell type may reflect antigen priming and subsequent loss of CD27 implying that antigen driven activation of specific T cell subsets may occur in pouchitis.