IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.

Objective: We sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis.

Design: Experimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation.

Morphometric Assessment of Confocal Laser Endomicroscopy for Pancreatic Ductal Adenocarcinoma, an Ex-Vivo Pilot Study.

Unlabelled: Ex-vivo freshly surgical removed pancreatic ductal adenocarcinoma (PDAC) specimens were assessed using pCLE and then processed for paraffin embeding and histopathological diagnostic in an endeavour to find putative image analysis algorithms that might recognise adenocarcinoma.

Methods: Twelve patients diagnosed with PDAC on endoscopic ultrasound and FNA confirmation underwent surgery. Removed samples were sprayed with acriflavine as contrast agent, underwent pCLE with an experimental probe and compared with previous recordings of normal pancreatic tissue.

Checkpoint Inhibitors.

Background: Treatment with checkpoint inhibitors such as anti-programmed death-1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibodies can prolong the survival of cancer patients, but it also induces autoimmune side effects in 86-96% of patients by activating the immune system. In 17-59% of patients, these are severe or even life-threatening.

Methods: This review is based on pertinent articles retrieved by a search in PubMed and on an evaluation of a side-effect registry.

The importance of pancreatic inflammation in endosonographic diagnostics of solid pancreatic masses.

Aims: Endosonography (EUS) is one of the main diagnostic tools for the differential diagnosis of pancreatic masses. The aim of our study was to describe the value of this technique in the work-up of solid pancreatic lesions, considering the influence of the morphological evidence of pancreatic inflammation in the diagnostic process.

Material And Methods: Retrospective analysis of prospectively collected data in our tertiary University center.

Modern Endoscopic Imaging in Diagnosis and Surveillance of Inflammatory Bowel Disease Patients.

Endoscopy remains the most important diagnostic and monitoring modality in the management of inflammatory bowel disease. Advances in imaging have progressively added new tools into the armamentarium of endoscopists with the goal of more accurate, sensitive, and accessible visual diagnoses for the benefit of patients with gastrointestinal diseases. Here, we review the relevant literature regarding commonly used endoscopic techniques (dye-based and digital chromoendoscopy, high-definition endoscopy, capsule endoscopy, and endosonography), as well as advanced and experimental technologies (full-spectrum endoscopy, endocytoscopy, autofluorescence, laser endoscopy, and endomicroscopy, including molecular imaging), applicable to inflammatory bowel diseases and emerging for implementation into everyday practice.

Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients.

Background: Endoscopic monitoring is fundamental for evaluating the therapeutic response in IBD, but a validated endomicroscopic mucosal healing (MH) score is not available to date. However, confocal laser endomicroscopy (CLE) might define MH more precisely than conventional endoscopy. The major aim was to establish and validate an MH score for ulcerative colitis (UC), based on CLE.

Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease.

Background & Aims: We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing.

Methods: Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon λ receptor 1 gene (Il28ra), and mice with disruption of the interferon regulatory factor 3 gene (Irf3), with or without disruption of Irf7 (Irf7). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression.

Anti-TNF-refractory colitis after checkpoint inhibitor therapy: Possible role of CMV-mediated immunopathogenesis.

Immune-related adverse events (irAEs) induced by checkpoint inhibitors are well known. Since fatal outcomes have been reported early detection and adequate management are crucial. In particular, colitis is frequently observed and can result in intestinal perforation.

Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With Ipilimumab.

Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients with metastatic melanoma. However, immune-related adverse effects occur in about 65% of ipilimumab-treated patients and have to be adequately managed. A 55-year-old patient developed grade 3 autoimmune colitis 7 weeks after initiation of ipilimumab treatment and subsequently hepatitis with grade 3 elevation of transaminases and γ-glutamyl transferase.

IL-9 and its receptor are predominantly involved in the pathogenesis of UC.

Objective: Several pathogenic roles attributed over the past two decades to either T helper (Th)1 or Th2 cells are increasingly becoming associated with interleukin (IL)-17 and most recently IL-9 signalling. However, the implication of IL-9 in IBD has not been addressed so far.

Design: We investigated the expression of IL-9 and IL-9R by using peripheral blood, biopsies and surgical samples.

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g.

In vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy.

Histiocytes have a pivotal role in wound repair and intestinal epithelial recovery - the most important goal to sustain gut functionality. Yet, an in vivo description of colonic histiocytes by confocal laser endomicroscopy (CLE) is missing. Here, we report the case of a 45-years-old male patient who was referred to our clinic with weight loss and a history of two consecutive Clostridium difficile colitis episodes, the latter cured 3 wk before present admission.

Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases.

Background: Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors.

Methods: Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity.

Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease.

The recent discovery and characterization of T helper 17 cells (Th17) and their signature cytokines (IL-17) represents a hallmark in T-cell immunobiology by providing a new distinctive pathway for the communication between adaptive and innate immunity. From the six members of the IL-17 cytokine family presently known, at least two have evident proinflammatory qualities and are involved in several chronic inflammatory disorders, including inflammatory bowel disease (IBD). IL-17A and IL-17F are abundantly found in inflamed IBD mucosa, suggesting their pivotal role in IBD.

The CD40-CD40L pathway contributes to the proinflammatory function of intestinal epithelial cells in inflammatory bowel disease.

In inflammatory bowel diseases (IBD), intestinal epithelial cells (IECs) are involved in the outbalanced immune responses toward luminal antigens. However, the signals responsible for this proinflammatory capacity of IECs in IBD remain unclear. The CD40/CD40L interaction activates various pathways in immune and nonimmune cells related to inflammation and was shown to be critical for the development of IBD.

Autoimmunity against type VII collagen in inflammatory bowel disease.

Autoimmunity against type VII collagen, an adhesion molecule of the extracellular matrix in epithelial basement membranes, is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). An intriguing association between EBA and inflammatory bowel disease (IBD) has been extensively documented over the last decades, but, because of the very low incidence of EBA, received little attention from physicians involved in the care of patients with IBD. More recently, autoantibodies against type VII collagen have been detected in up to 68% of IBD patients.

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis.

In contrast to healthy conditions, intestinal epithelial cells (IECs) stimulate proinflammatory CD4+ and CD8+ T cells during Crohn's disease (CD). The underlying regulatory mechanisms remain unknown. Here we investigated the epithelial expression of major histocompatibility complex (MHC) I and MHC II and its interference with endocytic pathways, in vivo.

Antigen targeting to MHC class II-enriched late endosomes in colonic epithelial cells: trafficking of luminal antigens studied in vivo in Crohn's colitis patients.

In Crohn's disease (CD), colonic epithelial cells (CECs) are suggested to stimulate pro-inflammatory CD4+ T cells. However, the endocytic pathways of luminal antigens involved in underlying MHC class II presentation by CECs remain unknown. Our aim was to elucidate antigen trafficking and associated MHC class II expression in CECs of CD patients in vivo.