See Dubinsky MC et al on page 1105 in CGH;See editorial on page 1038. Background & Aims:Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. ; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during followup. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true

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The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies.

No abstract

These data provide an important insight into the impact of epigenetic mechanisms in the pathogenesis of CD.

SUMMARYAnti-Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients [143 CD, 75 UC, 10 with indeterminate colitis (IC)] and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins ( Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in-house enzyme-linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA-positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease ( P < 0·001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years ( P < 0·0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.

Smoking habit influences the age at diagnosis and changes in disease extent in UC. Mechanisms are likely to be complex and require further investigation.

Smoking habit was associated with age at diagnosis and disease location in Crohn's disease, while disease location was associated with the rate of development of stricturing complications and requirement for surgery. The pathogenic basis of these observations needs to be explained.