Deficiency of fucosyltransferase 2 (FUT2) in humans which is involved in inducible fucosylation has been linked (by GWAS studies) to Crohn's disease (CD). GWAS analysis in patients with CD indicates that FUT2 loss is important for the disease development. However, about 20% of all humans lack FUT2 activity (termed 'non-secretors' as they do not fucosylate blood group antigens in the tissues and secretions, including saliva) and remain free of intestinal inflammation under steady state conditions. Thus, lack of fucosylation is likely not a causative, but a contributing factor in CD development. In this study, we will assess if fucosylation affects the severity of inflammation in patients with Crohn's disease.
Test if the disease severity and clinical outcome in patients with Crohn's disease is different in FUT2+ and FUT2- patients.
FUT2 positive and negative status will be assess by a previous GWAS study. Archived paraffin sections from ileal and colonic (control) biopsies from on qualified patients will be obtained for the detection of fucosylation with UEA-1 lectin by immunofluorescence. The intensity and distribution of UEA-1 lectin expression will be assessed in each sample.
Correlation will be made between FUT2 genotype, ileal fucosylation, histologic disease activity, endoscopic disease activity, and clinical disease activity. In order to assess the changes in fucosylation with time, ileal biopsies will be compared across multiple exams in the same patients and fucosylation compared with changes in histologic inflammation. In order to assess if fucosylation impacts disease-related outcomes, comparison will also be made between FUT2 genotype, ileal fucosylation, and disease severity as assessed by the number of Crohn's-related surgeries, time to progression to a second surgery after a first operation, number of Crohn's related hospitalizations, need for biologic therapy, average number of corticosteroid prescriptions per year, number of years in follow up with at least one recorded harvey bradshaw index >4, and percentage of endoscopic exams in endoscopic and histologic remission. In addition, patients who always remained in endoscopic and histologic remission will be compared to those who had disease activity at any point in follow up.
Inflammatory Bowel Disease Research in Progress Meeting occurring every other week; Dr. Pekow's laboratory meeting weekly; Dr. Alexander Chervonsky who will guide immunostaining work has laboratory meetings weekly.
| Scholarship & Discovery Tracks: | Basic/Translational Sciences, Clinical Research |
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| NIH Mission Areas: | NIDDK - Digestive |