602 research outputs found
Treatment Perspectives in Crohn’s Disease
Background: Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Summary: Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy
Innate and Adaptive Immunity in Inflammatory Bowel Diseases
While barrier function and the effects of the intestinal microbiome have only recently moved into the focus of inflammatory bowel disease research, the role of the innate and the adaptive immune system in these gastrointestinal disorders has extensively been studied. Although still not completely understood, the increasing knowledge about the immune system's contribution to the pathophysiology of inflammatory bowel diseases has led to new diagnostic and therapeutic approaches. This review gives a compact overview on this important topic
Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time
During the last decade, group-2 innate lymphoid cells (ILC2s) have been discovered and successfully established as crucial mediators of lung allergy, airway inflammation and fibrosis, thus affecting the pathogenesis and clinical course of many respiratory diseases, like for instance asthma, cystic fibrosis and chronic rhinosinusitis. As an important regulatory component in this context, the local pulmonary milieu at inflammatory tissue sites does not only determine the activation status of lung-infiltrating ILC2s, but also influences their motility and migratory behavior. In general, many data collected in recent murine and human studies argued against the former concept of a very strict tissue residency of innate lymphoid cells (ILCs) and instead pointed to a context-dependent homing capacity of peripheral blood ILC precursors and the inflammation-dependent capacity of specific ILC subsets for interorgan trafficking. In this review article, we provide a comprehensive overview of the so far described molecular mechanisms underlying the pulmonary migration of ILC2s and thereby the numeric regulation of local ILC2 pools at inflamed or fibrotic pulmonary tissue sites and discuss their potential to serve as innovative therapeutic targets in the treatment of inflammatory lung diseases
Confocal Laser Endomicroscopy for Diagnosis of Barrett’s Esophagus
Barrett’s esophagus (BE) is established as a premalignant condition in the distal esophagus. Current surveillance guidelines recommend random biopsies every 1–2 cm at intervals of 3–5 years. Advanced endoscopic imaging of BE underwent several technical revolutions within the last decade including broad-field (red-flag) techniques (e.g., chromoendoscopy) and small-field techniques with confocal laser endomicroscopy (CLE) at the forefront. In this review we will focus on advanced endoscopic imaging using CLE for the diagnosis and characterization of BE and associated neoplasia. In addition, we will critically discuss the technique of CLE and provide some tricks and hints for the daily routine practice of CLE for diagnosis of BE
Eosinophilic gastroenteritis with refractory ulcer disease and gastrointestinal bleeding as a rare manifestation of seronegative gastrointestinal food allergy
Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources. This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay. IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls. Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years. Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient
Advanced Endoscopic Imaging for Diagnosis of Crohn's Disease
Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to evaluate therapeutic success and for the surveillance of colitis associated cancer. Thus it becomes obvious that there is a need for new and more advanced endoscopic imaging techniques for better characterization of mucosal inflammation and early neoplasia detection in IBD. This paper describes the concept of advanced endoscopic imaging for the diagnosis and characterization of Crohn's disease, including magnification endoscopy, chromoendoscopy, balloon-assisted enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy
Reframing immune-mediated inflammatory diseases through signature cytokine hubs
No abstract available
Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis
Cryptococcus neoformans is an opportunistic fungal pathogen preferentially causing
disease in immunocompromised individuals such as organ-transplant-recipients,
patients receiving immunosuppressive medications or, in particular, individuals suffering
from HIV infection. Numerous studies clearly indicated that the control of C. neoformans
infections is strongly dependent on a prototypic type 1 immune response and classical
macrophage activation, whereas type 2-biased immunity and alternative activation
of macrophages has been rather implicated in disease progression and detrimental
outcomes. However, little is known about regulatory pathways modulating and balancing
immune responses during early phases of pulmonary cryptococcosis. Here, we analyzed
the role of group 2 innate lymphoid cells (ILC2s) for the control of C. neoformans
infection. Using an intranasal infection model with a highly virulent C. neoformans strain,
we found that ILC2 numbers were strongly increased in C. neoformans-infected lungs
along with induction of a type 2 response. Mice lacking ILC2s due to conditional
deficiency of the transcription factor RAR-related orphan receptor alpha (Rora) displayed
a massive downregulation of features of type 2 immunity as reflected by reduced
levels of the type 2 signature cytokines IL-4, IL-5, and IL-13 at 14 days post-infection.
Moreover, ILC2 deficiency was accompanied with increased type 1 immunity and
classical macrophage activation, while the pulmonary numbers of eosinophils and
alternatively activated macrophages were reduced in these mice. Importantly, this shift
in pulmonary macrophage polarization in ILC2-deficient mice correlated with improved
fungal control and prolonged survival of infected mice. Conversely, adoptive transfer
of ILC2s was associated with a type 2 bias associated with less efficient anti-fungal
immunity in lungs of recipient mice. Collectively, our date indicate a non-redundant role
of ILC2 in orchestrating myeloid anti-cryptococcal immune responses toward a disease
exacerbating phenotype
Complete Long-Term Remission of an Inflammatory Pseudotumor under Corticosteroid Therapy
Inflammatory pseudotumors (IPT) form a group of etiologically, histologically, and biologically heterogeneous tumefactive lesions that are histologically characterized by prominent inflammatory infiltrates. IPT has been described in various organs including the lungs, bladder, liver, spleen, heart, and others. It may mimic a malignant tumor clinically and radiologically. We report a case of a 26-year-old woman with an ALK1-negative IPT (7 cm in maximal diameter) mainly located in the 12th right back muscles, surrounding a fractured rib. Histologically, the tumor consisted of an inflammatory infiltrate composed predominantly of diffusely distributed lymphoplasmacytic cells and stromal fibroblasts associated with focal obliterative phlebitis. Conservative steroid treatment resulted in complete remission and the patient remained disease-free for more than 1 year later. To our knowledge this is the first report of IPT involving the skeletal back muscle and complete resolution under corticosteroid treatment
- …