Crypt Abscess

Abstract: To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse.

Abstract: Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell–specific deficiency of core 1–derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1–derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1–derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase–specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.

Abstract: Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.