Celiac Disease: Recent Research

[happygirl]

Rev Med Interne. 2007 Sep 17; [Epub ahead of print]

[stroke in young adults with celiac disease.][Article in French]

Audia S, Duch

[happygirl]

Clin Immunol. 2007 Oct 30; [Epub ahead of print]

Decreased circulating iNKT cell numbers in refractory coeliac disease.Bernardo D, van Hoogstraten IM, Verbeek WH, Pe

[happygirl]

Hepatology. 2007 Oct 29;46(5):1650-1658 [Epub ahead of print] Links

The liver in celiac disease.Rubio-Tapia A, Murray JA.

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN.

Celiac disease is a common (1% prevalence) chronic immune-mediated disorder of the small intestine induced by dietary wheat, barley, and rye. Several hepatic disorders have been described in association with celiac disease. Isolated hypertransaminasemia with nonspecific histologic changes in a liver biopsy is the commonest hepatic presentation of celiac disease. A gluten-free diet normalizes liver enzymes and histologic changes in most patients. Moreover, celiac disease can coexist with autoimmune liver disorders such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Celiac disease has increasingly been reported with a variety of other liver diseases. Thus, the hepatologist needs to consider celiac disease in the differential of abnormal liver blood tests and to be aware of the clinical implications of this frequent disease in patients with liver disorders. The possible mechanisms of liver injury and those common factors that explain the association of celiac disease with liver disorders are discussed. The aims of this article are (1) to review the spectrum and pathogenesis of liver injury related to celiac disease and (2) to provide direction to those caring for patients with chronic liver diseases regarding the detection and effective treatment of celiac disease. (HEPATOLOGY 2007;46:1650-1658.).

[happygirl]

Clin Gastroenterol Hepatol. 2007 Oct 27; [Epub ahead of print]Links

The MYO9B Gene Is a Strong Risk Factor for Developing Refractory Celiac Disease.Wolters VM, Verbeek WH, Zhernakova A, Onland-Moret C, Schreurs MW, Monsuur AJ, Verduijn W, Wijmenga C, Mulder CJ.

Department of Pediatric Gastroenterology, University Medical Centre Ultrecht, Utrecht.

BACKGROUND & AIMS: Celiac disease (celiac disease) is associated with HLA-DQ2 and HLA-DQ8 and has been linked to genetic variants in the MYO9B gene on chromosome 19. HLA-DQ2 homozygosity is associated with complications of celiac disease such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphoma (EATL). We investigated whether MYO9B also predisposes to RCD II and EATL. METHODS: Genotyping of MYO9B and molecular HLA-DQ2 typing were performed on 62 RCD II and EATL patients, 421 uncomplicated celiac disease patients, and 1624 controls. RESULTS: One single nucleotide polymorphism in MYO9B showed a significantly different allele distribution in RCD II and EATL patients compared with controls (P = .00002). The rs7259292 T allele was significantly more frequent in RCD II and EATL patients compared with celiac disease patients (P = .0003; odds ratio [OR], 3.61; 95% confidence interval [CI], 1.78-7.31). The frequency of the haplotype carrying the T allele of this single nucleotide polymorphism was significantly increased in RCD II and EATL patients (11%), compared with controls (2%) and celiac disease patients (3%) (OR, 6.76; 95% CI, 3.40-13.46; P = 2.27E-09 and OR, 4.22; 95% CI, 1.95-9.11; P = .0001, respectively). Both MYO9B rs7259292 and HLA-DQ2 homozygosity increase the risk for RCD II and EATL to a similar extent when compared with uncomplicated celiac disease patients (OR, 4.3; 95% CI, 1.9-9.8 and OR, 5.4; 95% CI, 3.0-9.6, respectively), but there was no evidence for any interaction between these 2 risk factors. CONCLUSIONS: We show that both MYO9B and HLA-DQ2 homozygosity might be involved in the prognosis of celiac disease and the chance of developing RCD II and EATL.

[happygirl]

Gut. 2007 Oct 26; [Epub ahead of print] Links

Interleukin-21 Contributes To The Mucosal T Helper Cell Type 1 Response In Celiac Disease.Fina D, Sarra M, Caruso R, Del Vecchio Blanco G, Pallone F, Macdonald TT, Monteleone G.

Italy.

BACKGROUND: In celiac disease (celiac disease), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon (IFN)-[gamma] and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T-bet and promote the Th1 cell response are unknown. OBJECTIVE: To examine whether interleukin (IL-)21, a cytokine that regulates T cell activation, has a role in celiac disease. SETTING: Duodenal mucosal samples were taken from celiac disease patients and normal controls. IL-21 and T-bet were examined by real-time PCR and Western blotting, and IFN-[gamma]was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL-21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated celiac disease patients. Finally, the role of IL-21 in controlling T-bet and IFN-[gamma] was also evaluated in cultures of biopsies taken from treated celiac disease patients and cultured with a peptic-tryptic digest of gliadin (PT) in the presence or absence of a neutralizing IL-21 antibody. RESULTS: Enhanced IL-21 RNA and protein expression was seen in duodenal samples from untreated celiac disease patients. Blockade of IL-21 activity in biopsies of untreated celiac disease patients reduced T-bet and IFN-[gamma] secretion. Stimulation of treated celiac disease biopsies with PT-gliadin enhanced IL-21 expression, and neutralization of IL-21 largely prevented PT-driven T-bet and IFN-[gamma] induction. CONCLUSIONS: IL-21 is over-produced in the mucosa of celiac disease patients, where it helps sustain T-bet expression and IFN-[gamma] production.

PMID: 17965065 [PubMed - as supplied by publisher]

[happygirl]

Diabetes Metab. 2007 Oct 25; [Epub ahead of print] Links

Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France.Poulain C, Johanet C, Delcroix C, L

[happygirl]

Arq Gastroenterol. 2007 Apr-Jun;44(2):156-61. Links

[serological screening of relatives of celiac disease patients: antiendomysium antibodies, anti-tissue transglutaminase or both?][Article in Portuguese]

Utiyama SR, Nass FR, Kotze LM, Nisihara RM, Ambrosio AR, Messias-Reason IT.

Laborat

[happygirl]

Ann Clin Biochem. 2007 Nov;44(Pt 6):537-43.Links

Antioxidant enzymes, glutathione and lipid peroxidation in peripheral blood of children affected by coeliac disease.Stojiljković V, Todorović A, Radlović N, Pejić S, Mladenović M, Kasapović J, Pajović SB.

Laboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Belgrade, Serbia.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of coeliac disease. The aim of this study was to examine the modulation of the biochemical response to oxidative stress in untreated and treated coeliac disease. METHODS: The study involved peripheral blood samples from 39 paediatric patients (18 with active, 11 with silent form of the disease, 10 on gluten-free diet [GFD]) and 30 control subjects. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentrations of total glutathione (GSH) and lipid hydroperoxides (LOOH) were determined in patients and controls. RESULTS: In comparison to the controls, a significant increase in SOD activity was found in the active group (P<0.05), while CAT activity was elevated in GFD group (P<0.05). GPx activity was lower in patients than in controls (active and silent, P<0.001; GFD, P<0.01). GSH contents were significantly reduced in all patient groups (P<0.001) as well, while the concentration of LOOH was elevated in active and silent group (P<0.001). The concentration of LOOH correlated negatively with the activity of GPx (r = -0.32, P<0.01) and the concentration of GSH (r = -0.70, P<0.001). A significant positive correlation was found between the concentration of GSH and the activity of GPx (r = 0.57, P<0.001). CONCLUSIONS: The results show evidence of increased oxidative stress in untreated coeliac disease. Although LOOH were not significantly elevated in the GFD group, changes in antioxidant enzyme activities and GSH content demonstrate that oxidative stress persists even in treated patients.

PMID: 17961308 [PubMed - in process]

[happygirl]

Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 19; [Epub ahead of print] Links

Is MYO9B the missing link between schizophrenia and celiac disease?Jungerius BJ, Bakker SC, Monsuur AJ, Sinke RJ, Kahn RS, Wijmenga C.

Complex Genetics Section, DBG‐Department Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

There has long been discussion on the correlation between schizophrenia and autoimmune diseases (especially celiac disease), which makes the recently discovered celiac disease risk factor, MYO9B, an attractive functional and positional candidate gene for schizophrenia. To test this hypothesis we compared allele frequencies of three MYO9B tag SNPs in 315 schizophrenia cases and 1,624 healthy controls in a genetic association study. Highly significant differences in allele frequencies between schizophrenia cases and healthy controls were observed for SNP rs2305767 in intron 14 of MYO9B (P = 1.16 x 10(-4); OR 1.41, 95% CI 1.18-1.67). We demonstrate significant association of allelic variants in MYO9B with schizophrenia. To our knowledge, this is the first molecular genetic evidence for a correlation between autoimmune diseases and the risk of developing schizophrenia. © 2007 Wiley-Liss, Inc.

PMID: 17948900 [PubMed - as supplied by publisher]

[happygirl]

Can J Gastroenterol. 2007 Oct;21(10):649-51.Links

Consumption of pure oats by individuals with celiac disease: A position statement by the Canadian Celiac Association.Rashid M, Butzner D, Burrows V, Zarkadas M, Case S, Molloy M, Warren R, Pulido O, Switzer C.

Dalhousie University, Halifax, Canada.

The treatment of celiac disease is a strict adherence to a gluten-free diet for life. In the past, oats were considered to be toxic to individuals with celiac disease and were not allowed in a gluten-free diet. However, recent evidence suggests that oats that are pure and uncontaminated with other gluten-containing grains, if taken in limited quantities, are safe for most individuals with celiac disease. For adults, up to 70 g (1/2 to 3/4 cup) of oats per day and for children, up to 25 g (1/4 cup) per day are safe to consume. These oats and oat products must fulfill the standards for a gluten-free diet set by the Canadian Food Inspection Agency and Health Canada. The Canadian Celiac Association, in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats. These strategies have led to the production of pure, uncontaminated oats for the first time in Canada. Oats and oat products that are safe for consumption by individuals with celiac disease and dermatitis herpetiformis are now commercially available in Canada.

PMID: 17948135 [PubMed - in process]

[happygirl]

Aliment Pharmacol Ther. 2007 Nov 1;26(9):1227-35. Links

A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease.Leffler DA, Edwards George JB, Dennis M, Cook EF, Schuppan D, Kelly CP.

The Celiac Center, Beth Israel Deaconess Medical Center, Department of Gastroenterology, Boston, MA, USA.

Background Increasing numbers of individuals are now being diagnosed with coeliac disease. The only accepted treatment for coeliac disease is lifelong adherence to a strict gluten-free diet (GFD). Individuals' ability to adhere to the GFD varies, but systematic studies guiding the assessment of adherence are currently lacking. Aim We sought to compare the predictive value of self-report and four serologic tests compared to expert nutritionist evaluation. Methods In all, 154 individual adults with biopsy-proven coeliac disease rated their adherence to the GFD on a Likert scale. Serum antibody titres of IgA anti-tissue transglutaminase, and IgA and IgG anti-deamidated gliadin peptides were determined. Using anova and ROC analyses, results were compared to a standardized evaluation by an expert nutritionist blinded to the participants' self-rated adherence and serology results. Results All serologic measures as well as participant reported adherence were significantly associated with GFD adherence as assessed by expert nutritionist evaluation. However, on ROC analysis no measure performed satisfactorily. The performance of serologic testing, but not self-report, improved with increased time on the GFD. Conclusion Although current serologic tests have very high sensitivities and specificities for the diagnosis of coeliac disease, they cannot replace trained nutritionist evaluation in the assessment of GFD adherence.

PMID: 17944737 [PubMed - in process]

[happygirl]

Aliment Pharmacol Ther. 2007 Nov 1;26(9):1217-25. Links

Increasing prevalence of coeliac disease over time.Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H, Lohi O, Bravi E, Gasparin M, Reunanen A, M

[happygirl]

Rheumatol Int. 2007 Oct 9; [Epub ahead of print] Links

Coeliac disease in systemic lupus erythematosus: a case report.Hrycek A, Siekiera U.

Department of Internal, Autoimmune and Metabolic Diseases, Medical University of Silesia, ul. Medyk

[happygirl]

Clin Gastroenterol Hepatol. 2007 Oct 3; [Epub ahead of print]Links

HLA DQ Gene Dosage and Risk and Severity of Celiac Disease.Murray JA, Moore SB, Van Dyke CT, Lahr BD, Dierkhising RA, Zinsmeister AR, Melton LJ 3rd, Kroning CM, El-Yousseff M, Czaja AJ.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.

BACKGROUND & AIMS: Celiac disease (celiac disease) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of celiac disease in an American population. METHODS: High-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with celiac disease and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk. Logistic regression modeling was used to examine the relative and absolute risks of celiac disease. RESULTS: Ninety-seven percent of celiac disease patients carried both of the HLA alleles, DQA1*05 and DQB1*02. Those who carried a second allele of DQB1*02 were 5 times more likely to have celiac disease than those with just one (95% confidence interval, 1.4-18.1). The carriage of 2 copies of DQB1*02 did not predict either an earlier age of onset or severity of disease. CONCLUSIONS: Both HLA alleles DQA1*05 and DQB1*02 are associated with a greatly increased risk of celiac disease, although the latter has the greater effect. Carrying 2 copies of DQB1*02 was associated with an even greater risk for disease but did not predict an earlier age of onset and diagnosis or disease severity. Assessing the copy number of the DQB1*02 allele might allow for the stratification of disease risk.

[happygirl]

Scand J Gastroenterol. 2007 Oct;42(10):1214-20. Links

Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls.Leeds JS, H

[happygirl]

Scand J Gastroenterol. 2007 Oct 5;:1-4 [Epub ahead of print] Links

Regression of lactose malabsorption in coeliac patients after receiving a gluten-free diet.Ojetti V, Gabrielli M, Migneco A, Lauritano C, Zocco MA, Scarpellini E, Nista EC, Gasbarrini G, Gasbarrini A.

Internal Medicine Catholic University, Rome, Italy.

Objective. In a recent study by our group, it was shown that a large proportion of patients with lactose malabsorption and with no bacterial overgrowth are affected by silent coeliac disease (celiac disease). Our aim was to evaluate the effect of a gluten-free diet on lactose malabsorption assessed using the hydrogen lactose breath test (LBT) and also the relationship with normalization of duodenal biopsies in coeliac patients. Material and methods. Fifteen patients (11 F, 4 M; mean age 35.8+/-6) affected by celiac disease with a positive LBT and negative glucose breath test were enrolled. All were started on a gluten-free diet and were re-evaluated after 6 months by LBT and after 12 months by both LBT and upper gastrointestinal endoscopy with biopsies. Results. LBT normalization was observed in 1 out of 15 patients (6.7%) after 6 months and in 9 of the remaining 14 (64.2%) after 12 months. Duodenal biopsies showed normal villi in 8 patients, partial villous atrophy in 5 and total atrophy in 2. Conclusions. The present study shows that a large proportion of celiac disease patients experience a regression of lactose malabsorption after receiving a gluten-free diet. This may be related to normalization of the brush border with an improvement of lactase enzyme activity. LBT should be performed after 12 months in celiac disease patients on a gluten-free diet in order to assess the persistence/disappearance of lactose malabsorption, thus avoiding an unnecessary lactose-free diet.

[happygirl]

J Trop Pediatr. 2007 Sep 30; [Epub ahead of print] Links

Prevalence of Celiac Disease, Helicobacter pylori and Gastroesophageal Reflux in Patients with Refractory Iron Deficiency Anemia.Fayed SB, Aref MI, Fathy HM, Dayem SM, Emara NA, Maklof A, Shafik A.

Departments of Pediatrics andClinical pathology, Al-Azhar, Cairo University and National Research Center, Cairo, Egypt.

Objective: The aim of this article is to determine the prevalence of celiac disease (celiac disease), Helicobacter pylori (H. pylori) and gastroesophageal reflux (GER) in patients with resistant iron deficiency anemia (IDA). Patients: The study included 25 patients <18 years of age with refractory IDA (not responding to iron therapy for 3 months in a dose of 6 mg elemental iron/kg/day). Methods: All patients included in the study were subjected to careful history taking and thorough clinical examination. Blood sample was taken for analysis of antibodies for celiac disease including: antigliadin antibody (AGA), antiendomysial antibody (EMA), antireticulin antibody (ARA) and antitissue Transglutaminase (tTg) IgG antibody. Anti-H. pylori IgG antibodies and a (13)C-urea breath test (UBT) was done to all patients to diagnose H. pylori. Upper gastrointestinal tract endoscopy was done for all patients to evaluate for the presence of some etiologies of intractable anemia as chronic blood loss. These included: celiac disease, H. pylori infection and GER. The upper gastrointestinal tract endoscopy was also done to evaluate the presence of bleeding spots, ulcers or angiomatous malformations. In addition, gastric antral biopsies were taken for diagnosis of H. pylori infection by the following tests: rapid urease test, histopathological examination and culture. Results: celiac disease was positive in 11 out of 25 patients (44%), H. pylori infection in 12 out of 25 patients (48%), while GER was diagnosed in 11 out of 25 patients (44%). Patients with celiac disease had age of presentation </=2 years in two patients (18.2%) while the remaining nine patients (81.8%) had age of presentation >2 years and it was statistically significant (p = 0.05*). Also patients with H. pylori had age of presentation </=4 years in five patients (41.7%) and the remaining seven patients (81.8%) had age of presentation >4 years and it was statistically significant (p = 0.03*). Logistic regression analysis demonstrated that the risk factors for severity of anemia were age of patients and duration of anemia. On the other hand, other parameters have no significant influence on the severity of anemia. Also risk factors of short stature were age of presentation of anemia, degree of anemia and H. pylori infection. AGA had the highest sensitivity (100%) followed by antiendomysium antibody (81.8%) while the tTG antibody had the highest specificity (85.7%) for diagnosis of celiac disease. UBT and histopathology had the highest sensitivity (100%) for diagnosis of H. pylori while rapid urease test, culture, H. pylori stool antigen and anti-H. pylori IgG antibody had the highest specificity (100%). In conclusion, refractory IDA may be due to clinically unapparent H. pylori gastritis and celiac disease. celiac disease is one of the most common causes of intestinal malabsorption during childhood which leads to impairment of iron absorption. Apart from offering them gluten-free diet rich in iron, early detection and treatment of IDA and prophylactic iron and folic acid supplementation will go a long way to optimize their mental and psychological functions. Eradication of H. pylori infection with concomitant iron therapy should correct the anemia.

PMID: 17908698 [PubMed - as supplied by publisher]

[happygirl]

Fetal Pediatr Pathol. 2007 May-Jun;26(3):125-34. Links

Celiac disease, pregnancy, small for gestational age: role of extravillous trophoblast.Hadziselimovic F, Geneto R, Buser M.

Kindertagesklinik Liestal, Liestal, Switzerland. faruk@magnet.ch

It is questionable whether development of the intrauterine growth retardation or small for gestational age (SGA) children is related directly to inflammation associated with celiac disease. Localization and the amount of gliadin, Fas-L, as well as the incidence of apoptosis in 32-term placentas, was analyzed immunohistochemically and with in situ hybridization in a blinded fashion; these were correlated with the weight of their newborns. Extravillous trophoblasts (EVTs) from the noncompliant women were overloaded with gliadin; there was a moderate amount or no gliadin present in the controls. The weight of newborns was lower if extravillous trophoblasts were loaded with gliadin (-2.24SD) (p = 0.004). Increased apoptosis of EVT in placentas of noncompliant women was consistent with abundant expression of Fas-L in those cells and was linked to the low birth weight of newborns. Exposure to gliadin alters extravillous trophoblast dynamics by causing an increase in apoptotic shedding. In genetically predisposed individuals, gliadin affects fetal part of the placenta causing children to be small for their age. A gluten-free diet during pregnancy prevents SGA children and, thus, the fetal origin of serious adult diseases.

[happygirl]

Scand J Gastroenterol. 2007 Jun 18;:1-5 [Epub ahead of print] Links

Gut microflora associated characteristics in first-degree relatives of children with celiac disease.Tjellstr