Pelvic ileo-anal reservoirs: a lectin histochemical study

Abstract

Pelvic ileo-anal reservoir (ileal pouch) formation is now a common surgical approach to the management of long-standing inflammatory bowel disease. The ileal mucosa in this new environment responds with changes in morphology and histochemical reactivity, as shown by conventional techniques. In this study, pre-pouch ileum and pouch ileal mucosa from 20 patients have been examined with a large panel of lectins using an avidin-biotin-peroxidase technique, with appropriate negative controls and sugar-inhibition studies. Changes were noted between pre-pouch ileum and the pouch mucosa which were complex, and no single alteration was seen in every case. Most variations related to saccharide sequences near the non-reducing termini of O- and N-linked glycans. Many of these were seen with lectins having requirements for terminal fucosyl residues, and to a lesser extent for galactosyl sequences, and were most obvious in the epithelium. Some of the changes occurred with such frequency as to suggest a direct response to surgery, but many of the variations were likely to be adaptive responses, possibly related to inflammation or infection. The changes in glycans were largely additive and could not be explained as a consequence of the actions of bacterial glycosidases. These alterations suggest that reservoir mucosa undergoes an adaptive response to the new intraluminal environment, without frank colonic metaplasia, and some changes occur to a greater degree in patients with pouchitis.

Mucin gene expression in the ileoanal reservoir is altered and may be relevant to the risk of inflammation and dysplasia

“…42 The anti-MUC1 and anti-MUC3 antibodies used in this study are directed against the VNTR peptide sequences of these genes and it is possible that glycosylation may affect the binding properties of antibodies. Glycosylation changes have been detected in IAR related to adaptation 43 and which occur without significant visible morphological modification. In UC, such differences in glycosylation are also apparent between groups of patients with similar and typical inflammatory bowel disease related morphology.…”

Pouches and Diverted Bowel

“…9 These alterations could well be the result of a change in bacterial flora. Colonic phenotypic change is supported by mucin histochemistry, 7,8 immunohistochemistry, 9,10 lectin histochemistry, 11 and mucin biochemistry. 12 Mucosal adaptive changes in ulcerative colitis pouches have been classified into 3 groups degree of inflammatory/ adaptive change is remarkably consistent both within individuals and with time.…”

Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation

“…Large bowel secreted mucins are rich in sulphated and O‐acetylated sialic acids, while small bowel shows lower sulphation and little O‐acetyl substitution of the sialic acids20, 21. These properties, together with lectin histochemistry of glycosylation patterns22, have allowed clear identification of small and large bowel mucins athistological and biochemical levels21, 23. The use of metabolic labelling has further supported histological analysis and provides information on synthesis, secretion, and turnover of mucins that cannot be obtained by other methods20, 24.…”

“…The use of metabolic labelling has further supported histological analysis and provides information on synthesis, secretion, and turnover of mucins that cannot be obtained by other methods20, 24. These techniques have shown that increased sulphation2, 3, 6, 24, O‐acetylation3, 5, and proximal colonic mucosal glycosylation22 occur early in the majority of ileoanal reservoirs, indicative of an adaptive change to a more colonic phenotype. This adaptation is further supported by decreased mucosal permeability and increased barrier function in healthy pouches.…”