Biochemical analysis of enzymic markers of inflammation in rectal biopsies from patients with ulcerative colitis and Crohn's disease.

Background: The diagnosis and monitoring of inflammatory bowel disease (IBD) has traditionally relied on clinical assessment, serum markers of inflammation and endoscopic examination. Fecal biomarkers such as calprotectin (FC) and lactoferrin (FL) are predominantly derived from neutrophils, are easily detectable in the feces and are now established as valuable markers of intestinal inflammation. In recent years, a ‘treat to target' concept has emerged for the management of IBD. Adequate control of inflammation in IBD at a biochemical level is quickly becoming an important target in IBD management. Key Messages: Fecal biomarkers have been shown to be significantly and consistently increased in both adult and pediatric patients with IBD versus those without IBD. Fecal biomarkers are therefore useful in determining those patients with gastrointestinal symptoms who are likely to benefit from colonoscopy versus those in whom colonoscopy is likely to be normal. Fecal biomarkers correlate significantly with endoscopic disease in both Crohn's disease and ulcerative colitis. Suggested cutoffs for FC for endoscopically active disease in IBD range from 50 to 280 μg/g. Fecal biomarkers reflect the success of treatment intensification and can help predict clinical relapse. Both FC and FL are accurate in the detection of postoperative endoscopic recurrence of Crohn's disease, and FC may be clinically useful in predicting those patients with acute severe ulcerative colitis who may progress to colectomy. There are limitations to these fecal tests including a false positive rate and intra-individual variability. Conclusions: This review focuses on the role of fecal biomarkers in the diagnosis, monitoring and management of IBD and how best to interpret results. We will discuss the emerging role of these biomarkers in the IBD management landscape including FC-guided drug dosing and the development of home-based testing and e-health applications. Fecal biomarker results must always be interpreted in a clinical context. Endoscopic assessment remains the gold standard for diagnosis and monitoring of IBD.

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Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis

Clinical Science ◽

10.1042/cs0830623 ◽

1992 ◽

Vol 83 (5) ◽

pp. 623-626 ◽

Cited By ~ 62

Author(s):

A. H. Raouf ◽

H. H. Tsai ◽

N. Parker ◽

J. Hoffman ◽

R. J. Walker ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Protein Content ◽

Bowel Disease ◽

Right Colon ◽

Control Subjects ◽

Inflammatory Bowel ◽

Rectal Biopsies

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis. 2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetyl-glucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetyIglucosamine incorporated into pure mucin was assessed. 3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305–0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959–1.111, P<0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378–0.829) did not quite reach statistical significance (P=0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetyl-glucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26). 4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618–1.022) than in their paired proximal colonic biopsies (0.602, 0.421–0.861; P<0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262–0.773; right colon: 0.470, 0.321–0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260–0.815; right colon: 0.492, 0.260–0.929, P = 0.8). 5. There was no significant difference in N-[3H]acetylglucosamine incorporation among the three groups (control subjects: 21195, 16611–32695 d.p.m./mg of biopsy protein content; ulcerative colitis: 12108, 7663-21 548 d.p.m./mg of biopsy protein content; Crohn's disease: 14 891, 8620-34 419 d.p.m./mg of biopsy protein content, P = 0.17), suggesting that there is a selective reduction of incorporation of sulphate per mucin side chain. 6. This study demonstrates a reduced ability of the rectal mucosa to sulphate mucin in patients with inflammatory bowel disease.

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