Transglutaminase, gluten and celiac disease: food for thought. Transglutaminase is identified as the autoantigen of celiac disease.
Explore the source record for details and available documents.
Autoantibodies↗
SEARCH · Search PubMed
Results for “CELIAC DISEASE”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Blockage of T-cell costimulation inhibits T-cell action in celiac disease.
BACKGROUND & AIMS: Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease. METHODS: Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. RESULTS: CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody. CONCLUSIONS: In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.
Abatacept↗
Celiac disease: a review.
Celiac disease is relatively rare in the United States and many of the facets of this complex disorder are not completely understood. In the gluten-sensitive individual, celiac disease is activated by ingestion of cereal glutens. An abnormal immune system response to dietary gluten causes damage to the small bowel mucosa, which results in nutrient malabsorption. When gluten is removed from the diet, malabsorption resolves. Nursing intervention in celiac disease requires careful nutritional assessment and dietary instruction.
Celiac Disease↗
Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease.
BACKGROUND & AIMS: Celiac disease appears to be a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. Duodenal biopsy specimens from patients with celiac disease and histologically normal controls were investigated to see if cytokine expression is related to disease activity. METHODS: Cytokine messenger RNA (mRNA) expression was determined by quantitative reverse-transcription polymerase chain reaction and in situ expression by immunohistochemistry. RESULTS: In normal controls, mRNA levels were usually below the quantitative limit, even after in vitro gluten stimulation. By contrast, interferon (IFN)-gamma mRNA was increased more than 1000-fold in untreated disease. In vitro gluten stimulation of specimens from treated patients (gluten-free diet) increased IFN-gamma mRNA to the levels of untreated patients. In addition, increased mRNA levels for interleukin (IL)-2, IL-4, IL-6, and tumor necrosis factor alpha were found after such stimulation, whereas mRNA for IL-5, IL-10, and IL-12p40 was usually below the quantitative level. Biopsy specimens from untreated patients contained on average 10-fold more lamina propria cells positive for IFN-gamma than normal controls, whereas cells containing IL-4 were rare in both subject groups. CONCLUSIONS: The results show that mucosal gluten exposure in patients with celiac disease rapidly elicits high levels of IFN-gamma expression and lower levels of IL-2, IL-4, IL-6, and tumor necrosis factor alpha even in the virtual absence of IL-12.
Adolescent↗
Systemic autoimmune disorders in celiac disease.
PURPOSE OF REVIEW: Celiac disease is an immune-mediated disorder clinically characterized by a multitude of symptoms and complications. The comorbidity between celiac disease and other autoimmune disorders has been clearly established. RECENT FINDINGS: Two main theories have been postulated to explain this comorbidity: (1) linkage disequilibrium between the genes responsible for celiac disease and those responsible for the coexpressed autoimmune diseases or (2) untreated celiac disease leading to the onset of other autoimmune diseases. This article reviews the current literature supporting either theory and places the current knowledge in the field within the context of the most recent data on the pathogenesis of celiac disease. SUMMARY: The current literature did not clearly establish which of the two theories explain the comorbidity between celiac disease and other autoimmune disorders. There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.
Animals↗
The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis).
BACKGROUND: The membrane bound receptor OX40 (CD134) - a member of the TNF-R/NGF-R superfamily - is expressed on activated CD4+-T cells in humans and rodents. The interaction of OX40 with its ligand (OX40L) has been shown to be important in T-cell dependent B cell-stimulation and T-cell costimulation in vitro and in vivo. Several studies in experimental animal models for immunologically mediated GI-diseases have stressed the important role of the OX40-OX40L interaction for their manifestations. To assess if the OX40-OX40L interaction is also crucial in the pathogenesis of immunologically mediated diseases of the human gastrointestinal tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated, in a first line of experiments, the expression of OX40 in biopsy specimens of patients suffering from these diseases. METHODS: The biopsies were formalin fixed and paraffin-embedded and cut into 5 microm slides. To demask the antigen, the slides were consecutively cooked in citrate buffer for 20 min. Binding of anti-OX40 antibody was detected using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. RESULTS: Nine of 11 biopsy specimens of patients with celiac disease were OX40-positive; none of the 20 control duodenal biopsies demonstrated OX40-positivity; and all biopsies of patients with ulcerative colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively for OX40. One of the 20 control biopsies showed OX40 staining. DISCUSSION: OX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.
Adolescent↗
Frequency and clinical pattern of celiac disease among siblings of celiac children.
To investigate the prevalence and clinical and genetic patterns of celiac disease (CD) among siblings of CD patients, 103 siblings and one twin of 80 celiac children were evaluated by means of their clinical history, physical examination, blood indices of nutritional status, and antigliadin antibodies (AGA). Antiendomysium antibody (AEA) levels were determined in 70 patients and 85 subjects were human leucocyte antigen (HLA) typed. On the basis of clinical or laboratory data or both, 21 siblings (20.2%) were submitted to intestinal biopsy, whereas intestinal biopsy in six siblings with positive serologic screening (AGA IgA or AEA or both) was not performed because of parental refusal. In a high percentage of cases (18%), all on a gluten-containing diet, the intestinal mucosa was atrophic, and CD was subsequently diagnosed. Because we could not submit all the siblings to intestinal biopsy, this figure could underestimate the real prevalence of the disease in our series; consequently, it was not possible to calculate accurately the sensitivity and specificity of AGA and AEA. Nevertheless, AEA (positive in all the nine siblings with mucosal atrophy), followed by AGA IgA, proved to be the best screening for CD. Eighteen of 19 CD siblings showed HLA-predisposing antigens. Among the 19 CD siblings, one showed a typical form with gastrointestinal symptoms, two had short stature, one suffered from recurrent vomiting, and in 15, the disease was clinically silent. On the contrary, among siblings who were first diagnosed (index cases), the majority (73.7%) had a typical form of CD, and no clinically silent cases were observed. We did not find any difference between index cases and CD siblings in food habits and distribution of HLA antigens. In 15 of 18 cases, the sibling diagnosed subsequently was the older one. Finally, the typical form of CD was significantly more frequent among the younger brother than the older. In conclusion, the high prevalence of the silent form of CD in our cases indicates that siblings of CD subjects should always be screened for CD. The combination of AGA IgA and AEA represent a good screening method to use in selecting children for the intestinal biopsy.
Celiac Disease↗
Studies of celiac disease. II. The apparent irreversibility of the proximal intestinal pathology in celiac disease.
Explore the source record for details and available documents.
Celiac Disease↗
Is celiac disease an autoimmune disorder?
Celiac disease, which results from an immune reaction to ingested cereal gluten proteins, has several autoimmune features. In particular, celiac disease patients produce highly disease specific IgA and IgG autoantibodies to tissue transglutaminase when they are on a gluten-containing diet, and they have small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen non-specific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial aetiology with complex genetics, and several autoimmune diseases are commonly presented by patients with celiac disease. Much has been learned about the immunology of celiac disease in recent years, and there is overwhelming evidence that the immune response to gluten is central to the pathogenesis. In light of this, the many autoimmune phenomena associated with celiac disease are thought-provoking, and they challenge us to rethink the boundaries between autoimmunity and immunopathology.
Autoantibodies↗
Celiac disease, posterior cerebral calcifications and epilepsy.
Ten patients (5 males) affected by epilepsy with cerebral calcifications of unknown etiology mainly located in the posterior regions were subjected to a battery of tests including an intestinal biopsy. Our aim was to establish whether or not the patients also suffered from celiac disease. Celiac diseases was found in 6 patients. This result and the individual cases reported in the literature suggest that this triad of diseases (celiac disease, posterior cerebral calcifications and epilepsy) are casually related. The same HLA phenotype was found in all 10 patients, i.e., including the cases without celiac disease, suggesting an underlying disorder of the immune system. Our results emphasize that particular attention should be paid to a search for celiac disease in all patients with epilepsy and posterior cerebral calcifications.
Adolescent↗
Celiac disease: fertility and pregnancy.
Celiac disease (gluten-sensitive enteropathy) may manifest clinically with an array of nongastrointestinal symptoms among which are: dermatitis herpetiformis; dementia; depression; various neurological symptoms; osteoporosis; osteomalacia; dental enamel defects, and anemia of various types. Important data have accumulated in recent years regarding the association between celiac disease, fertility and pregnancy. Many primary care obstetricians and gynecologists and perinatologists are not aware of these important relationships. The aim of this review, utilizing a MEDLINE search from 1966 through March 2000 of the English language, is to describe the possible effects of celiac disease and its treatment upon the reproductive cycle, fertility, pregnancy, and menopause. Review of the literature reveals that patients with untreated celiac disease sustain a significantly delayed menarche, earlier menopause, and an increased prevalence of secondary amenorrhea. Patients with untreated celiac disease incur higher miscarriage rates, increased fetal growth restriction, and lower birth weights. It appears that improvement of celiac disease, as reflected by restoration of small bowel mucosa associated with implementation of a gluten-free diet, may decrease miscarriage rates, improve fetal nutritional support and overall perinatal outcome.
Celiac Disease↗
Celiac disease and childhood stroke.
Celiac disease is associated with a diversity of central nervous system manifestations although an association with stroke has not been documented. This case report describes a child who presented with a recurrent transient hemiplegia. Magnetic resonance imaging of the brain confirmed infarction; transcranial Doppler studies and magnetic resonance angiography were abnormal. Although there were virtually no gastrointestinal symptoms and the child was thriving, celiac disease serology was strongly positive and a duodenal biopsy confirmed the disease. Tissue transglutaminase is the major autoantigen in celiac disease and is thought to maintain vascular endothelial integrity. Antiendomysial immunoglobulin A antibodies, demonstrated to be the same autoantibody as antitransglutaminase, react with cerebral vasculature, suggesting an autoimmune mechanism for celiac disease associated vasculopathy. Because celiac disease is a potentially treatable cause of cerebral vasculopathy, serology-specifically antitissue transglutaminase antibodies-should be included in the evaluation for cryptogenic stroke in childhood, even in the absence of typical gut symptoms.
Celiac Disease↗
In vitro mucosal digestion of synthetic gliadin-derived peptides in celiac disease.
Two celiac-active synthetic peptides derived from the A-gliadin structure corresponding to residues 8-19 (LQPQNPSQQQPQ) and to 11-19 were digested in vitro with small intestinal mucosa from children with celiac disease in remission and from normal children. The products of digestion were separated into two fractions on the basis of M(r) < 400 and M(r) > 400 by gel permeation chromatography and subjected to amino acid analysis. After digestion of the dodecapeptide with celiac mucosa, 71 +/- 14% (molar) of the total digestion products remained in the M(r) > 400 fraction. Glutamine, proline, serine, and asparagine were the major amino acids present. Glutamine, proline, and leucine were the major amino acids in the M(r) < 400 fraction. The M(r) > 400 fraction from the celiac mucosal digestion of the nonapeptide was of similar composition to the corresponding fraction from the dodecapeptide and represented 78 +/- 15% of the total products. Digestion of the two peptides with normal mucosa gave lower amounts of products in the M(r) > 400 fraction, but they were of similar composition to the corresponding fractions from the celiac mucosal digestion. Peptides such as NPSQQP and QNPSQQQ may be present in the M(r) > 400 fractions since glutamine and proline are present in the approximate ratio of 2:1, respectively. The results indicate a defect in the mucosal digestion of peptides which are active in an animal model of celiac disease.
Amino Acid Sequence↗
Concordance of dermatitis herpetiformis and celiac disease in monozygous twins.
Celiac disease can be defined as the classical manifestation of gluten sensitivity, which primarily affects the small intestine. Gluten sensitivity has also a skin manifestation, i.e., dermatitis herpetiformis. Both diseases have a strong genetic association with HLA DQ on chromosome 6. In this study we tried to estimate how much different clinical expressions of gluten sensitivity are determined by genetic factors, and hence how feasible they are for genetic mapping; therefore, we studied all six monozygous twin pairs found among 1292 prospectively collected patients of dermatitis herpetiformis in Finland. Three of the six twin pairs were concordant for dermatitis herpetiformis and for simultaneous enteropathy, celiac disease. Two other twin pairs were partially discordant, one of each pair had dermatitis herpetiformis and celiac disease, whereas the other had solely the gut manifestation of gluten sensitivity, i.e., celiac disease. Only one pair was found to be discordant for gluten sensitivity. All the pairs had typical risk alleles for gluten sensitivity, i.e., either HLA DQ2 or DQ8. These results demonstrate that the genetic component in gluten sensitivity as broadly defined is very strong (5/6 concordant). Genetically identical individuals can have clearly distinguished phenotypes, either dermatitis herpetiformis or celiac disease, suggesting that environmental factors determine the exact phenotype of this multifactorial disease. These findings are of importance in genetic linkage analyses, which focus to only certain phenotypic properties of a complex trait.
Adult↗
Celiac disease and recurrent pancreatitis.
BACKGROUND: Celiac disease is associated with pancreatico-biliary disease. Postulated mechanisms include reduced gallbladder emptying due to impaired cholecystokinin release and pancreatitis due to malnutrition. We hypothesize that celiac disease may also be associated with pancreatico-biliary abnormalities due to duodenal inflammation and papillary stenosis. METHODS: Over a 48-month period, 169 patients referred for possible sphincter of Oddi dysfunction who underwent pancreatico-biliary manometry were tested for gliadin and endomysial antibodies. Duodenal and papillary biopsies were preformed in those patients who were positive. RESULTS: Celiac disease was diagnosed in 12 (7.1%; 3 men, 9 women). The mean age was 61 years as compared with 37 years for those patients without celiac disease. All of the celiac patients had been referred for recurrent abdominal pain and/or idiopathic pancreatitis. Ten had idiopathic recurrent pancreatitis with elevated amylase and lipase levels. Two of these patients also had mildly elevated liver function tests associated with the abdominal pain. Only 3 of 12 patients had a prior diagnosis of celiac disease. These 12 patients had manometric evidence of stenosis and histologic evidence of periampullary inflammation as well as histologic changes consistent with celiac disease. In 10 of 12 patients sphincterotomy or extension of a prior papillotomy was performed. Two patients were treated with a gluten-free diet alone. CONCLUSIONS: We describe 12 patients with papillary stenosis and celiac disease. In 9 cases the celiac disease was a new diagnosis. Celiac disease should be considered in the etiology of papillary stenosis or idiopathic recurrent pancreatitis.
Adult↗
Prevalence of celiac disease in Turkish children.
BACKGROUND: Celiac disease has emerged as a public health problem, and the disease prevalence varies among different races and nations. The present study was designed to investigate the prevalence of celiac disease in apparently healthy Turkish schoolchildren and to detect children with silent celiac disease. METHODS: Healthy school children, 6 to 17 years of age, which there are 72,000 living in Erzurum were chosen as the study population. A total of 1,489 children were randomly selected by systematic sampling method. Samples were tested for anti- tissue transglutaminase IgA. Parents of the children who had positive test result were informed about the disease, and a small intestinal biopsy was proposed. A pathologist blinded to the serology results examined all biopsy specimens according to the modified Marsh criteria. RESULTS: A total of 1,263 healthy school children were screened for celiac disease. Of subjects, 687 (54.4%) were boys and 576 (45.6%) were girls. Mean age was 11.9+/-3.4 years (range, 6-17 years). None of the patients had IgA deficiency. Of 1,263 children, 11 had positive anti-tissue transglutaminase IgA. Thus, the total seropositivity was 0.87%. Of seropositive children, 6 (54.6%) were boys and 5 (45.4%) were girls. We calculated the prevalence of celiac disease as 1:115. The prevalence of biopsy proven celiac disease was 1:158. CONCLUSIONS: In this first celiac disease prevalence study in Turkey, we found that celiac disease is highly prevalent in healthy schoolchildren. Children with iron deficiency anemia and malnutrition should be evaluated more carefully with the understanding of the high celiac disease prevalence in Turkey.
Adolescent↗
Use of serological markers as a screening test in family members of patients with celiac disease.
That symptomatic celiac disease (CD) can occur in several members of a family has long been recognized. Given the possible complications of untreated CD, it is also important to diagnose those family members with "silent" disease, to offer them the benefit of a gluten-free diet. We studied 642 first-degree relatives of 210 patients with CD, two of the latter belonging to the same family. IgA and IgG antigliadin antibodies and IgA antiendomysium antibodies were studied in all. Jejunal biopsy was performed in 59 subjects, 47 with positive and 12 with negative serological markers. Celiac disease was diagnosed de novo in 18 cases (2.8%). Diagnosis in a symptomatic mother was made by jejunal biopsy despite the negativity of all immunological markers. We conclude that the risk of having CD is higher in siblings than in parents of patients with CD, that the most useful marker for diagnosis is the study of IgA antiendomysium antibodies, and that the absence of positive serological markers does not completely exclude the diagnosis of CD.
Adolescent↗
Endomysial antibodies as unreliable markers for slight dietary transgressions in adolescents with celiac disease.
Adolescents with celiac disease often fail to adhere to a strict gluten-free diet. The value of endomysial antibodies in assessing the dietary compliance of such adolescents has been assessed in 23 patients divided into four groups according to their daily gluten intake. Serum endomysial antibodies were absent in all subjects on a gluten-free diet and consistently present in those ingesting > 2 g/day of gluten. Only one of six and three of six teenagers with celiac disease with an intake of < 0.5 and 0.5-2 g/day, respectively, had endomysial antibodies in their serum, despite the presence in three of six and five of six of significant changes in the mucosal architecture, as shown by computerized morphometry of jejunal biopsies. In conclusion, endomysial antibodies cannot be considered a valid marker for slight dietary transgressions.
Adolescent↗