Tu1167 Determining the Treated Prevalence of Anxiety and Depression Using Administrative Data for Patients With IBD

Abstract

Background: It is well-recognized that Crohn's Disease (CD) has increased in incidence over the past decades. One explanation is that CD has evolved. We hypothesized that a specific, cellular readout that is based on CD pathology can be utilized to study the evolution of CD. We previously showed that in an animal model, the morphologic defects of ileal Paneth cell secretary granules (herein termed "Paneth cell phenotype") reflected interplay between genetic susceptibility and environmental triggers. In CD patients, Paneth cell phenotype was correlated with variants of susceptible genes ATG16L1 and NOD2. Excessive Paneth cell defects, defined as ≥20% of total Paneth cells showing abnormality (termed "bad" Paneth cell phenotype), was associated with a distinct gene expression profile, less likelihood of the presence of granuloma, and a more aggressive clinical outcome. Paneth cell phenotype is therefore an objective cellular readout to study the evolution of CD pathology. The goal of this study was to determine the Paneth cell phenotypes in various older and contemporary CD cohorts. Methods:We performed Paneth cell phenotype analysis using lysozyme immunofluorescence on uninvolved ileal sections from 124 consecutive adult CD resection cases collected between 2011 and 2013, and 35 consecutive pediatric resection cases collected between 2007 and 2009, all performed at a single institution (A institution cohort). The data were compared with Paneth cell phenotypes obtained from adult CD resection cases from two different institutions (each from a different time period): 1980-1982 (n=52; A cohort), and 1969-1977 (n=13; B institution cohort), and 42 pediatric CD biopsy cases collected between 2011 and 2013 (C institution cohort). Chi-square was performed for statistical analysis, with P<0.05 defined as significant. Results: In the contemporary adult CD cohort, 20 of the 124 cases (16%) possessed bad Paneth cell phenotype. This is in contrast to the two older adult cohorts, where only 2 of the 52 cases (3%) in the A institution cohort, and none of the cases in the B institution cohort showed bad Paneth cell phenotype (P=0.0252). The prevalence of bad Paneth cell phenotype in the contemporary pediatric CD patients was 47% (36 of 77 cases), also significantly greater than in the contemporary adult cohort (P<0.0001). In keeping with this finding, further analysis of the contemporary adult CD cases showed that all of the cases with bad Paneth cell phenotype had disease onset ≤ 30 years old (P=0.0194). Conclusions: Our findings suggest that CD with bad Paneth cell phenotype is more prevalent in pediatric than adult CD. This subtype of CD has appeared to emerge over the past 40 years. Future studies of the potential environmental trigger(s) in the cases with bad Paneth cell phenotype may provide insight into CD etiopathogenesis and rising incidence.