The identification of blood-derived response eQTLs reveals complex effects of regulatory variants on inflammatory and infectious disease risk.

Hundreds of risk loci for immune mediated inflammatory and infectious diseases have been identified by genome-wide association studies (GWAS). Yet, what causal variants and genes in risk loci underpin the observed associations remains poorly understood for most. The identification of colocalized cis-expression Quantitative Trait Loci (cis-eQTLs) is a promising way to identify candidate causative genes.

Lipopolysaccharide-binding protein in Crohn's disease patients: a promising noninvasive biomarker monitoring disease activity.

Background: Following STRIDE-II recommendations, the discovery of novel noninvasive biomarkers, beyond the use of C-reactive protein (CRP) and fecal calprotectin, remains a medical need to further improve the monitoring of patients with inflammatory bowel disease (IBD). This study aims to evaluate the potential of serum lipopolysaccharide-binding protein (LBP) in monitoring IBD activity.

Methods: This retrospective cross-sectional study included 69 IBD patients (43 Crohn's disease and 26 ulcerative colitis) and 82 controls.

Predictive models assessing the response to ustekinumab highlight the value of therapeutic drug monitoring in Crohn's disease.

Background: Despite the therapeutic efficacy of Ustekinumab (UST) in Crohn's disease (CD), loss of response (LOR) is observed over time. This study aims to evaluate the impact of the UST pharmacokinetics (PK) at induction on clinical and endoscopic outcomes, as well as to find predictive markers of UST response.

Methods: This retrospective study included 80 CD patients.

New approach to determine the healthy immune variations by combining clustering methods.

Immune-mediated inflammatory diseases are characterized by variability in disease presentation and severity but studying it is a challenging task. Defining the limits of a healthy immune system is therefore a prior step to capture variability in disease conditions. The goal of this study is to characterize the global immune cell composition along with their influencing factors.

N-acetylcysteine and glycyrrhizin combination: Benefit outcome in a murine model of acetaminophen-induced liver failure.

Background: Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries. Substantial progress has been made in understanding the mechanism of hepatocellular injury, but N-acetylcysteine remains the only effective treatment despite its short therapeutic window. Thus, other hepatoprotective drugs are needed for the delayed treatment of acetaminophen-induced hepatotoxicity.

New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.

Extracellular release of HMGB1 contributes to acetaminophen-induced liver injury. HMGB1 acts as a danger-associated molecular patterns during this toxic process but the mechanisms of action and targeted cells are incompletely defined. Here we studied, in vitro, the role of HMGB1 in amplifying the acetaminophen-induced hepatocyte necrosis process.

Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance.

Background: Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response.

Objective: The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response.

Patients And Methods: This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ.

Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn's Disease.

Background & Aims: A few rare monogenic primary immunodeficiencies (PIDs) are characterized by chronic intestinal inflammation that resembles Crohn's disease (CD). We investigated whether 23 genes associated with 10 of these monogenic disorders contain common, low-frequency, or rare variants that increase risk for CD.

Methods: Common and low frequency variants in 1 Mb loci centered on the candidate genes were analyzed using meta-data corresponding to genotypes of approximately 17,000 patients with CD or without CD (controls) in Europe.

Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis.

Background & Aims: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH.

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance.

Background: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure.

Type I interferon signaling in systemic immune cells from patients with alcoholic cirrhosis and its association with outcome.

Background & Aims: In immune cells, constitutively and acutely produced type I interferons (IFNs) engage autocrine/paracrine signaling pathways to induce IFN-stimulated genes (ISGs). Enhanced activity of IFN signaling pathways can cause excessive inflammation and tissue damage. We aimed to investigate ISG expression in systemic immune cells from patients with decompensated alcoholic cirrhosis, and its association with outcome.