Alterations in mucosal content of colonic glycoconjugates in inflammatory bowel disease defined by monoclonal antibodies

Abstract

The presence of several glycoconjugates in colonic mucosa of patients with inflammatory bowel disease was assessed through indirect immunofluorescent staining using a collection of 23 monoclonal antibodies directed against human colonic mucin glycoproteins (anti-HCM MAbs). Intensity and distribution of staining by three anti-HCM MAbs were significantly altered in mucosa from patients with ulcerative colitis (UC) (n = 14) when compared with normal tissue (n = 15) and with tissue from patients with Crohn's disease as well as other inflammatory disorders (n = 15). Staining by anti-HCM MAb 17, which binds to colonic mucin glycoprotein species IV and V, was absent or diminished in 86% of samples from patients with active UC in contrast to 14% of normal and disease control specimens. Reduction in anti-HCM MAb 17 staining was less marked in mucosal biopsy specimens from patients with UC lacking acute inflammatory activity (n = 8). In contrast to the apparent loss of the MAb 17-defined epitopes, staining with anti-HCM MAbs 10 and 22 was enhanced in UC tissue compared with normal and disease controls. Increased staining with MAb 10 was present in 93% of samples from UC patients demonstrating active inflammation. Increased MAb 10 staining was not apparent in noninvolved mucosa from UC patients, indicating that increased expression of the specified epitope is related to the acute inflammatory process. In contrast, indirect immunofluorescent staining with MAb 22 was apparent in both involved (78%) and uninvolved (67%) UC mucosa in contrast to normal and disease controls (less than 12%). In addition, staining with several other anti-HCM MAbs (MAbs 3, 11, 15) was modestly and variably diminished (14%-28%) in UC, Crohn's disease, and other inflammatory disorders. These findings demonstrate the presence of alterations in mucosal content of specific glycoconjugate structures in association with UC. Inflammatory processes may also result in broad changes in glycoconjugate determinants generally.