Search

The integrated haplotype score method is employed for a complete evolutionary, as well as functional analysis of the risk loci of the celiac disease. The analyses prove that SH2B3 plays an extremely significant factor for protecting people against bacterial infection.

Increased intestinal permeability (IP) has emerged recently as a common underlying mechanism in the pathogenesis of allergic, inflammatory, and autoimmune diseases. The characterization of zonulin, the only physiological mediator known to regulate IP reversibly, has remained elusive. Through proteomic analysis of human sera, we have now identified human zonulin as the precursor for haptoglobin-2 (pre-HP2). Although mature HP is known to scavenge free hemoglobin (Hb) to inhibit its oxidative activity, no function has ever been ascribed to its uncleaved precursor form. We found that the single-chain zonulin contains an EGF-like motif that leads to transactivation of EGF receptor (EGFR) via proteinase-activated receptor 2 ([PAR.sub.2]) activation. Activation of these 2 receptors was coupled to increased IP. The siRNA-induced silencing of [PAR.sub.2] or the use of [PAR.sub.2.sup.-/-] mice prevented loss of barrier integrity. Proteolytic cleavage of zonulin into its [[alpha].sub.2]- and [beta]-subunits neutralized its ability to both activate EGFR and increase IP. Quantitative gene expression revealed that zonulin is overexpressed in the intestinal mucosa of subjects with celiac disease. To our knowledge, this is the initial example of a molecule that exerts a biological activity in its precursor form that is distinct from the function of its mature form. Our results therefore characterize zonulin as a previously undescribed ligand that engages a key signalosome involved in the pathogenesis of human immune-mediated diseases that can be targeted for therapeutic interventions. autoimmune diseases | epidermal growth factor receptor | gut permeability | proteinase-activated receptor 2 | celiac disease

Celiac disease (CD) is an autoimmune inflammatory disease with a relatively high prevalence especially in the western hemisphere. A strong genetic component is involved in the pathogenesis of CD with virtually all individuals that develop the disease carrying HLA-DQ alleles that encode specific HLA-DQ2 or HLA-DQ8 heterodimers. Consumption of cereals rich in gluten triggers a chronic intestinal inflammation in genetically susceptible individuals leading to the development of CD. Emerging evidence has implicated a central role for IL-15 in the orchestration and perpetuation of inflammation and tissue destruction in CD. Therefore, IL-15 represents an attractive target for development of new therapies for CD. Transgenic mice that express human IL-15 specifically in enterocytes ([T3.sup.b]-hIL-15 Tg mice) develop villous atrophy and severe duodeno-jejunal inflammation with massive accumulation of NK-like [CD8.sup.+] lymphocytes in the affected mucosa. We used these mice to demonstrate that blockade of IL-15 signaling with an antibody (TM-[beta]1) that binds to murine IL-2/IL-15Rbeta (CD122) leads to a reversal of the autoimmune intestinal damage. The present study, along with work of others, provides the rationale to explore IL-15 blockade as a test of the hypothesis that uncontrolled expression of IL-15 is critical in the pathogenesis and maintenance of refractory CD. autoimmunity | celiac disease | immunotherapy | interleukine 15 receptor

This study investigates whether non-HLA loci are shared by type 1 diabetes and celiac disease, which have a common genetic origin. The results indicate that both type 1 diabetes and celiac disease share common alleles, and might exhibit common biological mechanisms.

The pathogenesis, diagnosis, and management of the celiac disease, a unique autoimmune disorder in which the environmental precipitant, gluten is known is reviewed.

Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement [...]

Byline: Adi Vaknin (1), Rami Eliakim (2), Zvi Ackerman (3), Israel Steiner (1) Keywords: celiac disease; neurological abnormalities; epilepsy; immune mediated peripheral neuropathy; down syndrome Abstract: Abstract Background Celiac disease (CD) is a gluten-sensitive enteropathy in genetically susceptible individuals. Anecdotal reports suggest that the nervous system might be affected in the disorder, but the severity and prevalence of such an involvement have not been systematically evaluated. Materials and methods Analysis of files of CD patients diagnosed between 1980 and 1999 for neurological abnormalities. Diagnosis of CD was based on the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition. Results Of 148 CD patients, 18 (12%) had 21 neurological disorders that could not be attributed to any other condition including muscle abnormality (3), epilepsy (3), psychiatric disease (4), peripheral neuropathy (3), cerebrovascular disease (1), myelopathy (1) and Down syndrome (2). Other disorders probably unrelated to CD were present in 8 patients. Conclusion If this association is not coincidental, both the central and the peripheral nervous systems may be affected in CD by a spectrum of neurological disorders that are either the outcome of CD or share the same pathogenesis with the enteropathy. Author Affiliation: (1) Department of Neurology, Hadassah University Hospital, Jerusalem, Israel (2) Department of Gastroenterology, Rambam Medical Center, P. O. Box 960, Haifa, 31096 (3) Department of Medicine, Hadassah Mount Scopus Hebrew University, Hadassah Medical School, Jerusalem, Israel Article History: Registration Date: 01/01/2004 Received Date: 12/10/2003 Accepted Date: 10/05/2004

For celiac disease (CD) a genome search has been made using 281 markers on 110 affected sib pairs and their parents. First systematic linkage analysis was performed on 39 pairs in which both sibs had symptomatic CD. Replication of regions of interest was performed on 71 pairs in which one sib had a silent form and the other one had a symptomatic one. It appears that, in addition to the HLA risk factors, which are well known, a risk factor in 5qter is involved in both types of CD and that a factor on 11qter may differentiate the two. No region implicated recently in the literature was found to be associated.

Celiac disease (CD) is an intestinal malabsorption syndrome in which diarrhea, malnutrition, and bleeding are common. CD is reversed by removal of gluten-containing cereals from the diet. CD has a genetic component that has been associated with several histocompatibility antigens. These are specific proteins present on most cells in the body. Their presence is controlled by genes that code for them, and they recognize 'self' tissues for the immune system. Thus, transplantation of foreign tissue presents new antigens to the immune system, and antibodies against the new antigens are promptly made. Human antigens are called human leukocyte (white blood cell) antigens (HLA) and different HLA subsets are associated with the occurrence of many diseases. The relationship between the subclass HLA (class II), HLA-DP, and coeliac disease, as well as the association with insulin-dependent diabetes mellitus (IDDM) and dermatitis herpetiformis (DH, another gluten-related disease), was studied in 254 subjects with these diseases or who were in a family with CD. The results confirmed previous studies which showed that people with CD frequently had an alteration in the alpha portion of the HLA-DP structure. Further, people with DH also tended to have this alteration, although less often, while people with IDDM and healthy subjects did not. An additional alteration in the beta portion of HLA-DP was found in people with CD; many of the CD patients with the alpha alteration had the beta alteration. Alterations in HLA-DP alpha structure were not associated with particular forms of two other class II HLA proteins, HLA-DR and HLA-DQ. Further, some CD patients did not possess the HLA-DP alpha alteration. The study indicates that susceptibility to CD may be related to more than one HLA characteristic, or to a complex mixture of HLA factors. (Consumer Summary produced by Reliance Medical Information, Inc.)

* Context.--Celiac sprue affects genetically susceptible individuals, who develop small intestinal injury and malabsorption following dietary exposure to gluten. The histologic features are nonspecific but characteristic. Objectives.--To outline the histologic features of celiac sprue and the necessary clinical context to permit a diagnosis of celiac sprue, to assist the pathologist to identify artifactual biopsy changes that may mimic sprue, to define the differential diagnosis for conditions with a similar histology, and to review historic investigations of this disease. Data Sources.--Sources include the historic experiments and clinical work of members of the Gastroenterology Division of the Department of Medicine and experiences with gastrointestinal pathology consultation material at the University of Washington, Seattle, with reference to selected peer-reviewed articles. Conclusions.--Confirmation of a diagnosis of celiac sprue is 2-fold: first, biopsy evidence of a characteristic, but nonspecific, pattern of injury including villous blunting or flattening, surface enterocyte damage, and increased intraepithelial lymphocytes; and second, dramatic clinical response to a gluten-free diet. Complete gluten removal from the diet is effective treatment for patients with symptoms of malabsorption; however, lifelong adherence to the diet is expensive, socially limiting, and nearly impossible on a contemporary diet with manufactured foodstuffs. Therefore, pathologists should avoid overdiagnosis of celiac disease based on minimal, nonspecific histologic changes. (Arch Pathol Lab Med. 2008;132:1594-1599), Celiac sprue (CS) is a complex multigenic disease. Genetically susceptible individuals may develop small intestinal injury and malabsorption from dietary exposure to "gluten" proteins in wheat, barley, and rye. Confirmation [...]

A new mixture of selected sourdough lactobacilli and fungal proteases is used to eliminate the toxicity of wheat flour during long-time fermentation. It is considered as an efficient approach to eliminate gluten toxicity.

A study is conducted on the celiac disease, which is an autoimmune disease occurring in genetically pre-disposed individuals as the result of an immune response to gluten, and the therapy for the same. It is seen that a gluten-free diet where wheat, rye, and barley is to be avoided, will be one of the important therapies.

Abstract Background--Coeliac disease is characterised by increased epithelial renewal associated with a mucosal T cell response to gliadin. Keratinocyte growth factor (KGF) is produced by cytokine activated gut stromal cells [...]

Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single- nucleotide polymorphisms [G/T.sub.-13910] and [G/A.sub.-22018] upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls. In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population. European Journal of Clinical Nutrition (2012) 66, 1364-1365; doi: 10.1038/ejcn.2012.153 Keywords: celiac disease; primary lactase deficiency; children 2 (2.2) 1 (0.6) NS 2 (2.2) 1 (0.6) NS, INTRODUCTION Lactose intolerance is a clinical syndrome, including abdominal pain, diarrhea, nausea, flatulence and/or bloating, after the ingestion of lactose or lactose-containing food substances. (1) Primary lactase deficiency (PLD) is [...]