INFLAMMATORY BOWEL DISEASE

Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients

K Bodger¹, J Halfvarson², A R Dodson³, F Campbell³, S Wilson⁴, R Lee⁴, E Lindberg², G Järnerot², C Tysk², J M Rhodes¹

¹ School of Clinical Science, University of Liverpool, Liverpool, UK
² Örebro University Hospital, Örebro, Sweden
³ Pathology Department, Royal Liverpool University Hospital, Liverpool, UK
⁴ Histochemistry Research Unit, University of Southampton, UK

Correspondence to:
Professor J M Rhodes
School of Clinical Science, University of Liverpool, Daulby St, Liverpool L69 3GA, UK; rhodesjm{at}liverpool.ac.uk

Background and aims: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose ß1, 3 N-acetylgalactosamine -), among the same IBD twins.

Materials and methods: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn’s disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor B (NFB) activation with investigators blinded to the diagnosis.

Results: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p = 0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFB.

Conclusions: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFB activation.

Abbreviations: IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; NFB, nuclear factor B; TF, Thomsen-Friedenreich; PNA, peanut lectin

Keywords: colitis; Crohn’s disease; glycosylation; inflammatory bowel disease; mucin; twins

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