eQTL in diseased colon tissue identifies novel target genes associated with IBD.

Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci.

Machine Learning-Based Prediction Models for Clostridioides difficile Infection: A Systematic Review.

Introduction: Despite research efforts, predicting Clostridioides difficile incidence and its outcomes remains challenging. The aim of this systematic review was to evaluate the performance of machine learning (ML) models in predicting C. difficile infection (CDI) incidence and complications using clinical data from electronic health records.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

Background & Aims: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD.

Methods: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort).

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

Introduction: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity.

The FOXP3 Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease.

Background & Aims: The incidence of Crohn's disease (CD) continues to increase worldwide. The contribution of CD4 cell populations remains to be elucidated. We aimed to provide an in-depth transcriptional assessment of CD4 T cells driving chronic inflammation in CD.

Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease.

Background: Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).

Aim: To test whether PRS indicates PSC risk in patients with IBD.

Non-Invasive markers of inflammation and protein loss augment diagnosis of celiac disease.

Background: Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity.

Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn's Disease.

Background: The development of Crohn's disease [CD] involves immune cell signalling pathways regulated by epigenetic modifications. Aberrant DNA methylation has been identified in peripheral blood and bulk intestinal tissue from CD patients. However, the DNA methylome of disease-associated intestinal CD4+ lymphocytes has not been evaluated.

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

Objective: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in ().

Design: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed.

Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis.

Background: Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC.

Methods: A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs.

Durable Response in Patients With Refractory Fistulizing Perianal Crohn's Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial.

Background: Refractory perianal Crohn's disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose-derived mesenchymal stem cells.

Objective: This study aimed to assess therapeutic safety and feasibility in the completed STOMP (stem cells on matrix plugs) phase 1 clinical trial.

G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.

Background & Aims: Although T-cell intrinsic expression of G9a has been associated with murine intestinal inflammation, mechanistic insight into the role of this methyltransferase in human T-cell differentiation is ill defined, and manipulation of G9a function for therapeutic use against inflammatory disorders is unexplored.

Methods: Human naive T cells were isolated from peripheral blood and differentiated in vitro in the presence of a G9a inhibitor (UNC0642) before being characterized via the transcriptome (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin by sequencing), protein expression (cytometry by time of flight, flow cytometry), metabolism (mitochondrial stress test, ultrahigh performance liquid chromatography-tandem mas spectroscopy) and function (T-cell suppression assay). The in vivo role of G9a was assessed using 3 murine models.

Rhamnose Is Superior to Mannitol as a Monosaccharide in the Dual Sugar Absorption Test: A Prospective Randomized Study in Children With Treatment-Naïve Celiac Disease.

Background And Aim: We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation.

Methods: We prospectively randomized children undergoing endoscopy with abnormal ( = 54) and normal ( = 10) concentrations of circulating antibodies to tTG, to either L:M or L:R.

Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex.

Background & Aims: Biliary disease is associated with a proliferative/fibrogenic ductular reaction (DR). p300 is an epigenetic regulator that acetylates lysine 27 on histone 3 (H3K27ac) and is activated during fibrosis. Long non-coding RNAs (lncRNAs) are aberrantly expressed in cholangiopathies, but little is known about how they recruit epigenetic complexes and regulate DR.

Vulvar Crohn's Disease: Clinical Features and Outcomes.

Introduction: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown.

Methods: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers.

Regulation and Role of αE Integrin and Gut Homing Integrins in Migration and Retention of Intestinal Lymphocytes during Inflammatory Bowel Disease.

Targeting interactions between α4β7 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses αEβ7 integrin, which is expressed on proinflammatory lymphocytes, to increase cell retention. The factors governing lymphocyte migration into the intestinal mucosa and αE integrin expression in healthy subjects and IBD patients remain incompletely understood.

Perianal magnetic resonance imaging findings and their potential impact on outcome in children with perianal fistulizing Crohn disease.

Background: Children with perianal fistulizing Crohn disease require intensive medical management but also have a higher risk for subsequent surgical interventions.

Objective: We performed a retrospective study to identify patient factors and perianal anatomical features by pelvic MR that are associated with surgical interventions in these children.

Materials And Methods: We included children with Crohn disease and perianal fistula who underwent pelvic MR with available, archived images and collected demographic, clinical and laboratory data.