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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 β1, 3 N-acetylgalactosamine α-), 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 κB (NFκB) 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 NFκB 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 NFκB. 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’ NFκB activation. [ABSTRACT FROM AUTHOR]

Abstract: Background.: CARD15/NOD2 polymorphisms are associated with Crohn''s disease. There is a high concordance for disease and disease phenotype in monozygotic twin pairs with Crohn''s disease. Aim.: We studied CARD15/NOD2 polymorphisms in a Swedish, population-based cohort of monozygotic twins with Crohn''s disease to assess whether these variants explain disease concordance. Subjects and methods.: Twenty-nine monozygotic twin pairs (concordant n =9, discordant n =20) with Crohn''s disease and 192 healthy controls were investigated for the CARD15/NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC. Results.: CARD15/NOD2 mutations were found in 5/38 (13%) twins with Crohn''s disease, corresponding to a total allele frequency of 6.6%. Only 2/9 concordant twin pairs carried any of the variants and the remaining seven were wild type genotype. The total allele frequency was 4.4 times higher (95% confidence interval 1.0–21.5, p =0.06) in concordant twins than in discordant ones, 11.1% versus 2.5%. In healthy controls the total allele frequency was 2.6%. Conclusions.: CARD15/NOD2 polymorphisms contribute but do not alone explain concordance of Crohn''s disease in monozygotic twins and, at least in a Swedish population, other polymorphisms are required. The low occurrence of CARD15/NOD2 mutations in the study and other Northern European populations suggests that these variants are of less importance in Northern Europe. [Copyright &y& Elsevier]

Background and aims: An increased occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) is reported in unaffected members of families with Crohn's disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population. Patients and methods: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD 15/NOD2 genotype. Results: ASCA were more common in Crohn's disease than in ulcerative colitis (40/70(57%) twins v 5/43 (12%) twins). Associations with ileal Crohn's disease, stricturing/penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn's disease compared with 7/27(26%) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn's disease, in monozygotic (ICC = -0.02) or dizygotic (ICC = -0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn's disease (ICC = 0.76). Conclusions: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn's disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn's disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenolypic characteristics. [ABSTRACT FROM AUTHOR]