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

Keith Bodger ¹, Jonas Halfvarson ², Andrew Dodson ³, Fiona Campbell ³, Susan Wilson ⁴, Ronald Lee ⁴, Eva Lindberg ², Gunnar Jarnerot ², Curt Tysk ² and Jonathan Rhodes ^1*

¹ University of Liverpool, United Kingdom
² Orebro University Hospital, Sweden
³ Royal Liverpool University Hospital, United Kingdom
⁴ University of Southampton, United Kingdom

^* To whom correspondence should be addressed. E-mail: rhodesjm{at}liverpool.ac.uk.

Accepted 21 December 2005

Abstract

Background / 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 1,3 N-acetylgalactosamine -), among the same IBD twins.

Materials & Methods: Formalin-fixed, paraffin- embedded, rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included 8 UC twin pairs and 14 Crohn's disease (CD) twin pairs with 6 pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for NFkappaB activation with investigators blinded for diagnosis.

Results: Unaffected twins were almost all TF positive (15/16) compared with 5/29 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 the glycosylation changes are acquired rather than genetically determined. Activated NFkappaB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but only 6/22 histologically normal controls (P=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFkappaB.

Conclusions: Altered mucosal glycosylation in unaffected identical twins of IBD patients is confirmed. This occurs in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "pre-inflammatory" NFkappaB activation.

Keywords: Crohn's, colitis, glycosylation, inflammatory bowel disease, mucin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller and Alastair Watson
Gut 2006 55: 905. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Guzman-Aranguez, A., Mantelli, F., Argueso, P. (2009). Mucin-type O-glycans in Tears of Normal Subjects and Patients with Non-Sjogren's Dry Eye. IOVS 50: 4581-4587 [Abstract] [Full Text]  
• Knight, P., Campbell, B. J., Rhodes, J. M. (2008). Host-bacteria interaction in inflammatory bowel disease. Br Med Bull 88: 95-113 [Abstract] [Full Text]  
• Rhodes, J. M (2007). The role of Escherichia coli in inflammatory bowel disease. Gut 56: 610-612 [Full Text]