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049 ALTERED COLONIC GLYCOPROTEIN EXPRESSION IN UNAFFECTED MONOZYGOTIC TWINS OF INFLAMMATORY BOWEL DISEASE PATIENTS
K. Bodger1, A.R. Dodson2, C. Tysk3, F. Campbell2, E. Lindberg3, G. Järnerot3, J.M. Rhodes1. Depts of1Medicine and2Pathology, University of Liverpool, UK;3Orebro Medical Centre Hospital, Orebro, Sweden
Introduction: Alterations in epithelial glycoprotein expression in inflammatory bowel disease (IBD) include increased expression of the oncofetal carbohydrate antigens, TF (galactose β1,3Nacetylgalactosamine) and sialyl-Tn (sTn, sialyl 2,6Nacetylgalactosamine). Previous chromatographic colonic mucin analysis in monozygotic twins with IBD suggested a possible genetic basis for these changes (Tysk et al, Gastroenterology 1991;100:419). The present study aimed to explore this further by assessing mucosal expression of specific glycoprotein epitopes amongst IBD twins.
Methods: Formalin-fixed rectal biopsies from 22 monozygotic twin pairs with IBD were studied (6 pairs concordant for UC or CD; 16 healthy twins). Affected twins were in clinical and endoscopic remission. Expression of sTn and TF was assessed by indirect immunohistochemistry using a specific monoclonal antibody and peanut lectin respectively, and compared with expression in rectal biopsies from normal mucosa (irritable bowel syndrome) controls (n=14 sTn; n=17 TF) with investigators blinded for diagnosis. TF positivity was scored from 0 to 3.
Results: Compared to histologically normal controls, unaffected twins showed significantly greater TF positivity and a trend towards greater sTn positivity (table⇓).
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Of the 5 unaffected twins who were sTn positive, 4 had twins with UC and 1 with CD. One of the sTn-positive/TF positive healthy twins has subsequently developed UC.
Conclusions: The positive findings in unaffected twins support previous evidence of a biochemical mucin defect. This could be the result either of a direct genetically determined alteration in glycosylation or of a secondary, eg cytokine-mediated, alteration in glycosylation. The altered glycosylation could be relevant in determining changes …