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

Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients
Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients
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 ?1, 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 (NF?B) 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 NF?B 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 NF?B.

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” NF?B activation.

0017-5749
973-977
Bodger, K.
616f8fc6-d211-461c-889a-ff26f5488363
Halfvarson, J.
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Dodson, A.R.
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Campbell, F.
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Wilson, S.J.
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Lee, R.
3dcb7598-d8d0-495a-9309-44eb609d72b1
Lindberg, E.
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Järnerot, G.
a7675a30-dd4c-404a-ab04-367b42ba32c5
Tysk, C.
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Rhodes, J.M.
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Bodger, K.
616f8fc6-d211-461c-889a-ff26f5488363
Halfvarson, J.
e1d466c3-4790-4e5a-ab49-9f15dfa3665f
Dodson, A.R.
42bff5d8-086a-40e0-9882-6d079be6c3f2
Campbell, F.
a0f36565-1a39-4aeb-8e77-54c7134f2b19
Wilson, S.J.
21c6875d-6870-441b-ae7a-603562a646b8
Lee, R.
3dcb7598-d8d0-495a-9309-44eb609d72b1
Lindberg, E.
94996fc4-3dea-404a-8f00-eb6fc6c327fd
Järnerot, G.
a7675a30-dd4c-404a-ab04-367b42ba32c5
Tysk, C.
941d7310-f82a-41cc-b7ff-296832b577af
Rhodes, J.M.
cc07f4c1-fb78-4433-8d8e-e2fa8d2318e4

Bodger, K., Halfvarson, J., Dodson, A.R., Campbell, F., Wilson, S.J., Lee, R., Lindberg, E., Järnerot, G., Tysk, C. and Rhodes, J.M. (2006) Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients. Gut, 55 (7), 973-977. (doi:10.1136/gut.2005.086413). (PMID:9428217)

Record type: Article

Abstract

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 ?1, 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 (NF?B) 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 NF?B 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 NF?B.

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” NF?B activation.

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Published date: July 2006

Identifiers

Local EPrints ID: 190907
URI: http://eprints.soton.ac.uk/id/eprint/190907
ISSN: 0017-5749
PURE UUID: 5982cd83-0acd-40ac-ac0d-c9ee0deb7b45

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Date deposited: 16 Jun 2011 10:48
Last modified: 16 Jul 2019 23:27

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Contributors

Author: K. Bodger
Author: J. Halfvarson
Author: A.R. Dodson
Author: F. Campbell
Author: S.J. Wilson
Author: R. Lee
Author: E. Lindberg
Author: G. Järnerot
Author: C. Tysk
Author: J.M. Rhodes

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