Increased development of T-bet+CD11c+ B cells predisposes to lupus in females: Analysis in BXD2 mouse and genetic crosses.

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ follicular T-helper cells. IFN-ß was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family.

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a low-fat chow diet (CD, n = 663) or a high-fat diet (HFD, n = 685). We further generate key metabolic data in a parallel cohort euthanized at four time points. HFD feeding shortens lifespan by 12%: equivalent to a decade in humans. Initial body weight and early weight gains account for longevity differences of roughly 4-6 days per gram. At 500 days, animals on a HFD typically gain four times as much weight as control, but variation in weight gain does not correlate with lifespan. Classic serum metabolites, often regarded as health biomarkers, are not necessarily strong predictors of longevity. Our data indicate that responses to a HFD are substantially modulated by gene-by-environment interactions, highlighting the importance of genetic variation in making accurate individualized dietary recommendations.

P009 Assessing the Status Quo: Ulcerative Colitis Monitoring in a Community GI Practice.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is a life-long condition with a relapsing and remitting course. As with other chronic diseases, close monitoring of UC is essential to achieving desired outcomes. Given the progressive nature of IBD and its corresponding complexities of care, monitoring of these diseases can be optimized in a collaborative, IBD-focused care center. Currently, there is no standard of care for disease monitoring in IBD. Society guidelines and the STRIDE program have recommendations on the use of patient reported outcomes (PRO), biomarkers, and endoscopy in disease monitoring. The purpose of this study is to assess the utilization of current guideline recommendations for the monitoring of UC in a community GI practice. METHODS: This study is a single-center, retrospective chart review of adult patients with moderate-severe UC receiving infusion-based drugs infliximab (IFX) or vedolizumab (VDZ) starting in January 2019. We performed a literature review of the most recent society guidelines on UC management and the STRIDE program's treat-to-target recommendations for UC. Study domains were chosen based on STRIDE targets. Twelve guidelines and recommendations were chosen for assessment based on feasibility of chart review. Demographic, treatment, and outcomes variables were collected. Data was extracted at time points relative to induction start date. RESULTS: Twelve gastroenterologists provided care for the 39 patients that met inclusion criteria. Ten patients received IFX and 29 received VDZ. All patients had documented PROs at weeks 0, 6, and 14; however, there was inter and intra-provider variability in descriptors and detail of documented PROs. A CRP was drawn prior to induction therapy, at week 6, and at week 14 or later in maintenance, 97.4%, 80%, and 87.2% of the time, respectively. A fecal calprotectin was drawn prior to induction therapy, at week 6, and at week 14 or later in maintenance, 71.8%, 41.0%, and 62.0% of the time, respectively. All patients had a colonoscopy performed prior to induction. These were performed greater than 1 year prior to induction (33.3%), between 6-12 months prior (7.7%), and within 6 months (59.0%). Only 19 (48.7%) patients had post-induction colonoscopy performed by the end of the study period. These colonoscopies were performed within 6 months of induction start (47.4%), between 6-9 months (27.8%), and after 9 months (27.8%). The overall rate of follow-up colonoscopy in the post-induction period of 9 months was 36.0%. Of the 58 colonoscopies performed, 51.7% had a documented Mayo score. CONCLUSION: Current guidelines offer recommendations on the use of PROs, biomarkers, and endoscopy in monitoring ulcerative colitis. This study highlights the presence of inconsistency in the use of these monitoring tools. When growing an IBD care center, it is necessary to identify strengths and weaknesses of the existing types and processes of care. When this care is not standardized, there in inevitably increased variability in provider care, as is evident by the results of this study. A well-defined methodology for monitoring patients with IBD should be defined and implemented to improve outcomes and stimulate growth in IBD care centers.