1,720,994 research outputs found
Intraepithelial lymphocytes in celiac disease immunopathology
No full textCeliac disease is a T cell-mediated immune disorder induced by dietary gluten that is characterized by the development of an inflammatory anti-gluten CD4 T cell response, anti-gluten antibodies, and autoantibodies against tissue transglutaminase 2 and the activation of intraepithelial lymphocytes (IELs) leading to the destruction of the intestinal epithelium. Intraepithelial lymphocytes represent a heterogeneous population of T cells composed mainly of cytotoxic CD8 T cells residing within the epithelial layer, whose main role is to maintain the integrity of the epithelium by eliminating infected cells and promoting epithelial repair. Dysregulated activation of IELs is a hallmark of CD and is critically involved in epithelial cell destruction and the subsequent development of villous atrophy. In this review, we compare and contrast the phenotype and function of human and mouse small intestinal IELs under physiological conditions. Furthermore, we discuss how conditions of epithelial distress associated with overexpression of IL-15 and non-classical MHC class I molecules induce cytotoxic IELs to become licensed killer cells that upregulate activating NKG2Dand CD94/NKG2C natural killer receptors, acquiring lymphokine killer activity. Pathways leading to dysregulated IEL activation could eventually be targeted to prevent villous atrophy and treat patients who respond poorly to glutenfree diet. © Springer-Verlag 2012
How Future Pharmacologic Therapies for Celiac Disease Will Complement the Gluten-Free Diet
Full text linkThe only proven treatment for celiac disease is adherence to a strict, lifelong, gluten-free diet. However, complete dietary gluten avoidance is challenging and a substantial number of patients do not respond fully, clinically, or histologically, despite their best efforts. As celiac disease is common and its central pathophysiology is well elucidated, it has become attractive for drug development to address the limitations of dietary treatment. Most efforts address nonresponsive celiac disease, defined as continued symptoms and/or signs of disease activity despite a gluten-free diet, and the more severe forms of refractory celiac disease, types I and II. An increasing spectrum of therapeutic approaches target defined mechanisms in celiac disease pathogenesis and some have advanced to current phase 2 and 3 clinical studies. We discuss these approaches in terms of potential efficiency, practicability, safety, and need, as defined by patients, regulatory authorities, health care providers, and payors
Does gluten intake influence the development of celiac disease-associated complications?
No full textCeliac disease (CD) is regarded as the most common autoimmune enteropathy in western countries. Epidemiological studies indicate that approximately 1:100 individuals may present with histologically proven CD. CD develops in genetically predisposed subjects after gluten ingestion. It usually subsides after gluten is withdrawn from their diet. Gluten is the only known environmental factor that affects the progression/regression of the intestinal villous atrophy, which is the hallmark of this disease. CD generally follows a benign course after gluten elimination. However, it is also associated with the development of other autoimmune disorders or of intestinal malignancies. The issue of whether such complications, sometimes of significant clinical and prognostic impact, are or are not the result of ongoing gluten ingestion, is an important one that has been investigated over the recent years with conflicting results. In terms of practical implications, the presence of a positive correlation between gluten intake and the development of severe complications would lead to the need for early diagnosis and mass screening. The lack of such correlation would instead suggest a less aggressive diagnostic strategy. This review aims at critically summarizing the evidence supporting either hypothesis. Copyright © 2013 by Lippincott Williams &Wilkins
Extra-Intestinal Manifestations of Coeliac Disease in Children: Clinical Features and Mechanisms
Full text linkCeliac disease (CD) is a systemic autoimmune disease due to a dysregulated mucosal immune response to gluten and related prolamines in genetically predisposed individuals. It is a common disorder affecting ~1% of the general population, its incidence is steadily increasing. Changes in the clinical presentation have become evident since the 80s with the recognition of extra-intestinal symptoms like short stature, iron deficiency anemia, altered bone metabolism, elevation of liver enzymes, neurological problems. Recent studies have shown that the overall prevalence of extra-intestinal manifestations is similar between pediatric and adult population; however, the prevalence of specific manifestations and rate of improvement differ in the two age groups. For instance, clinical response in children occurs much faster than in adults. Moreover, an early diagnosis is decisive for a better prognosis. The pathogenesis of extra-intestinal manifestations has not been fully elucidated yet. Two main mechanisms have been advanced: the first related to the malabsorption consequent to mucosal damage, the latter associated with a sustained autoimmune response. Importantly, since extra-intestinal manifestations dominate the clinical presentation of over half of patients, a careful case-finding strategy, together with a more liberal use of serological tools, is crucial to improve the detection rate of CD
In a large Juvenile Idiopathic Arthritis (JIA) cohort, concomitant celiac disease is associated with family history of autoimmunity and a more severe JIA course: a retrospective study
Full text linkBackground: A higher prevalence of celiac disease (CD) has been reported in patients with juvenile idiopathic arthritis (JIA) compared to the general population. Factors related to the increased risk of co-occurrence and associated disease course have not been fully elucidated. Aims of this study were to determine the prevalence of CD in a large Southern Italian cohort of children with JIA, describe their clinical features and disease course and investigate risk factors associated with their co-occurrence. Findings: Demographic, clinical and laboratory data of all patients with JIA admitted to our Pediatric Rheumatology Unit from January 2001 to June 2019, who underwent CD screening, were retrospectively extracted from clinical charts and analyzed. Eight of 329 JIA patients were diagnosed with CD, resulting in a prevalence higher than the general Italian population (2.4% vs 0.93%, p < 0.05). Familiarity for autoimmunity was reported by 87.5% patients with JIA and CD compared to 45.8% of those without CD (p < 0.05). 87.5% patients with JIA and CD required both a conventional Disease Modifying Anti-Rheumatic Drug (DMARD) and a biological DMARD over time compared to 36.4% of those without CD (p < 0.05). Conclusion: A higher CD prevalence was found in a large JIA cohort, supporting the need for CD screening in all JIA children, especially those with a family history of autoimmunity, found to be associated with the co-occurrence of the two diseases. This is clinically relevant since patients with CD and JIA more often required a step-up therapy, suggesting a more severe JIA clinical course
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