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Objective: In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients., Material and Methods: We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life., Results: The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients., Conclusions: NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.

Unlabelled: Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100-200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential., Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted.

In celiac disease, the gut-associated immune system is activated in response to the ingestion of gluten, causing an atrophy of the small intestinal mucosa. Although this condition is, in most cases, responsive to a gluten-free diet, celiac disease refractory to treatment occurs in a small percentage of celiacs. An epithelial barrier defect is known to be an integral part of celiac pathophysiology. However, the mucosa in refractory celiac disease underlies a constant inflammatory process. The epithelial barrier has not been addressed in this condition so far. Herein, the tight junction-associated barrier in refractory celiac disease is investigated functionally and structurally. Although normally expressed in celiac disease, claudin-4 is shown to be downregulated in refractory cases, presumably by two mechanisms, reduced protein expression and increased claudin endocytosis. Furthermore, the tightening claudin-5 is downregulated and the pore-forming claudin-2 is upregulated., (© 2012 New York Academy of Sciences.)

Celiac disease is a common autoimmune disease affecting 1% of the Western populations. It is an inappropriate immune response, in genetically susceptible patients to dietary wheat, rye, barley and oats. Treatment involves a Lifelong gluten-free diet that predisposes to low compliance due to limited variety, high cost and low palatability, imposing social pressure and affecting quality of life. The result is an urgent need for alternative therapeutic strategies. Based on the growing actual knowledge on the intestinal inflammatory cascade, mucosal immunology and genetics of celiac disease, new attractive potential therapies are emerging. Possibilities include: searching for low immunogenic wheat variants or strains pretreated with enzymes or binders for lower toxicity. Other strategies involve decreasing transepithelial uptake or dampening of the adaptive immune response by transglutaminase inhibitors or blockage of the HLA groove and immune modulation to shift the TH1 to TH2 profile. Developing biological therapy aims to decrease intestinal homing, adhesion and activity of inflammatory cells, counteract the pro-inflammatory cytokines, clonal intestinal T cells or mesenchymal stem cell replacement or mitogenic intestinal repair safety, cost, affordability and clinical effectiveness are of prime concern. Most of the above strategies showed promising results ex-vivo. The future will highlight the in-vivo winner.

Celiac disease (CD) is one of the most common immune-mediated diseases with a worldwide prevalence of around 1%, although a couple of decades ago the disease was thought to be very rare. CD is characterized by an inadequate inflammatory response to gluten in genetically susceptible individuals. In this inflammatory response both the adaptive and innate immunity are involved. The clinical picture of CD is variable ranging from severe malabsorption syndrome to silent cases. Disease specific antibodies can aid in selecting patients for a small intestinal biopsy, which is thought to be the gold standard investigation to diagnose CD. However, in selected patients, serology can be sufficient to confirm the diagnosis and a biopsy is not needed. Hitherto, the only treatment for CD is adherence to a lifelong strict gluten-free diet. The purpose of this review was to summarize current literature on the epidemiology and pathophysiology of CD and to discuss diagnostic and therapeutic approaches.

Delayed sexual maturation is a known complication of celiac disease (CD). There is paucity of data regarding the effect of gluten-free diet (GFD) on sexual maturity in patients with CD in India. We did a cross-sectional observational study to assess the sexual maturity in 30 adolescents with CD on GFD for at least 1 year, and evaluated factors which affect their sexual maturity. Sexual maturation was assessed using Tanner's stages of sexual development. All adolescents had completed 2 years of GFD and 53 % had completed 4 years of GFD. Sexual maturation was delayed in 30 %. Age at initiation of GFD was associated with attaining appropriate sexual maturity (p = 0.048). We conclude that delayed sexual maturation is not uncommon in adolescents with CD and may be corrected by early diagnosis and initiation of GFD.

Objective: The clinical presentation of coeliac disease has changed and patients are often overweight at diagnosis. There is concern that patients might gain further weight while on a gluten-free diet (GFD). The aim of the study was to evaluate the impact of a GFD on the body mass index (BMI) in a nationwide cohort of coeliac patients and to determine variables predictive of favourable or unfavourable BMI changes., Methods: We prospectively investigated weight and disease-related issues in 698 newly detected adults diagnosed due to classical or extraintestinal symptoms or by screening. BMI at diagnosis and after one year on a GFD were assessed and compared with that in the general population., Results: At diagnosis, 4% of subjects were underweight, 57% normal, 28% overweight and 11% obese. On a GFD, 69% of underweight patients gained and 18% of overweight and 42% of obese lost weight; in the rest BMI remained stable. Changes were similar in both symptom- and screen-detected patients. The coeliac group had a more favourable BMI pattern than the general population. Favourable BMI changes were associated with subjects' self-rated expertise on GFD and young age at diagnosis, but not dietary counselling received., Conclusions: BMI improved similarly in screen- and symptom-detected coeliac disease patients on a GFD., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This article explores possible relationships between migraine, irritable bowel syndrome (IBS), celiac disease (CD), and gluten sensitivity. These seemingly distinct medical entities curiously share many common epidemiological, psychosocial, and pathophysiological similarities. Considerable evidence is emerging to support a concept that experiencing significant threatening adverse events creates a state of hypervigilance in the nervous system, which associates with exaggerated response to future threats and episodic attacks of migraine and IBS. While this sensitizing response is generally considered to reside in the central nervous system, it may be possible that the initiation resides in the enteric nervous system as well. What appears to link migraine, IBS, and CD is a disease model of a genetically sensitive nervous system transformed into one that is hypervigilant, and that over time can often develop disabling and pervasive disease.

Objectives: In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances., Methods: Forty-five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x-ray absorptiometry, were obtained., Results: Patients after 1 year of receiving GFD had higher BMD z scores compared with baseline (-1.45 ± 0.28 vs -0.61 ± 0.25, respectively, P = 0.004). BMD z scores were significantly lower than expected for the normal population, after 1 (P = 0.03) or at least 2 (P < 0.001) years of receiving GFD. In group B, BMD z score was positively correlated with 25-hydroxy vitamin D levels (P = 0.009). In the repeated measurements group, 25-hydroxy vitamin D differed between pre- and post-GFD (P = 0.018). No biochemical index was capable of predicting an abnormal BMD z score (receiver operating characteristic curve analysis, all of the areas under the curve <0.66)., Conclusions: GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x-ray absorptiometry should be included in the standard management of children with CD.

Background: The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5-10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up., Aim: This study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors., Materials and Methods: The files of all children diagnosed with type 1 diabetes mellitus from 2003-2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized., Results: Forty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements., Conclusion: Physicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Background and Aim: Celiac patients report fatigue and reduced social activities, which may decrease physical activity. This study investigated the physical activity, fatigue and bone mineral density in celiac women at diagnosis and during diet., Materials and Methods: The first group (n=48) had the bone mineral density measured at diagnosis and after 2 years of a gluten-free diet; in the second group (n=47) bone mineral density was measured at diagnosis and after 5 years of a gluten-free diet. Both groups completed a physical activity questionnaire and visual analogue scale for the perception of fatigue at diagnosis and follow-up. Data about smoking habits, alcohol use, presence of gastrointestinal symptoms, drug therapy and body mass index were also collected., Results: At diagnosis, the two groups were similar for all considered variables. At follow-up, the mean body mass index and physical activity questionnaire's score were similar to baseline. The bone density increased in both groups, whilst the physical activity questionnaire and visual analogue scale remained unchanged., Conclusion: The improvement in bone density following a gluten-free diet was significant after 2 years; physical activity is frequently low and plays a minor role in determining the changes in bone mineral density., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality and healthcare costs in the western world. Although smoking is an important trigger of COPD, other factors such as chronic inflammation and malnutrition are known to influence its development. Because coeliac disease (CD) is characterized both by dysregulated inflammation and malnutrition, the possibility of an association between CD and COPD was investigated., Methods: Through biopsy data from all Swedish pathology departments, we identified 10 990 individuals with CD who were biopsied between 1987 and 2008 (Marsh 3: villous atrophy). As controls, 54 129 reference individuals matched for age, sex, county and calendar year of first biopsy were selected. Cox regression analysis was then performed to estimate hazard ratios (HRs) for having a diagnosis of COPD according to the Swedish Patient Register., Results: During follow-up, 380 individuals with CD (3.5%) and 1391 (2.6%) controls had an incident diagnosis of COPD, which corresponds to an HR of 1.24 (95% CI: 1.10-1.38) and an excess risk of COPD of 79/100 000 person-years in CD. The risk increase remained 5 years after biopsy (HR = 1.17; 95% CI: 1.00-1.37). Risk estimates did not change with adjustment for type 1 diabetes, thyroid disease, rheumatoid arthritis, country of birth or level of education. Men with CD were at a higher risk of COPD (HR = 1.39; 95% CI: 1.18-1.62) than women with CD (HR = 1.11; 95% CI: 0.94-1.30). Of note, CD was also associated with COPD before CD diagnosis (odds ratio = 1.22; 95% CI: 1.02-1.46). Conclusion.  Patients with CD seem to be at a moderately increased risk of COPD both before and after CD diagnosis., (© 2011 The Association for the Publication of the Journal of Internal Medicine.)

Scope: The main objectives of this study were to estimate dietary fumonisin exposure and nutrient intake in a group of patients diagnosed with celiac disease compared to non-celiac subjects., Methods and Results: The fumonisin level in 118 frequently consumed corn-based products was determined and dietary habits were recorded using a 7-day weighed food record. Data were then compared to those obtained for a control group. The fumonisin intake in the celiac patients was significantly higher than in controls, with mean values (± SE) of 0.395 ± 0.049 and 0.029 ± 0.006 μg/kg body weight per day, respectively. With regard to nutritional habits, celiac patients showed a preference for a high fat diet, coupled with a high intake of sweets and soft drinks and a low intake of vegetables, iron, calcium and folate., Conclusion: These findings may have serious health implications for the celiac population due to the widespread occurrence of fumonisins in most of the widely consumed gluten-free products, leading to continuous exposure to this particular mycotoxin. Moreover, the recorded nutritional quality of the celiac patient's diet raises concerns regarding its long-term adequacy and its potential impact on chronic conditions such as type 2 diabetes and cardiovascular diseases., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: The clinical presentations of celiac crisis and refeeding syndrome in celiac disease are almost similar, but information about refeeding syndrome is scarce. We are reporting for the first time 5 cases of refeeding syndrome in children with celiac disease that could have otherwise been labeled as celiac crisis., Methods: From January to December 2010, a chart review of hospital records of all celiac disease cases was performed, and refeeding syndrome was ascribed in those celiac patients who deteriorated clinically after initiation of a gluten-free diet and had biochemical parameters suggestive of refeeding syndrome such as hypophosphatemia, hypokalemia, hypocalcemia, and hypoalbuminemia., Results: Of the total 35 celiac disease patients, 5 (median age 6.5 [range 2.2-10] years, 3 boys) were identified as having refeeding syndrome. All 5 children were severely malnourished (body mass index <14 kg/m) and all of them had anemia, hypophosphatemia, hypokalemia, hypoalbuminemia, and hypocalcemia, meaning that they had the perfect setting for developing refeeding syndrome. At the same time, their clinical features fulfilled the criteria for celiac crisis except that their symptoms have worsened after the introduction of a gluten-free diet. Nevertheless, instead of using steroids, they were managed as refeeding syndrome in terms of correction of electrolytes and gradual feeding, and that led to a successful outcome in all of them., Conclusions: Severely malnourished patients with celiac disease are at risk of developing potentially life-threatening refeeding syndrome, which may mimic celiac crisis, especially in developing countries. Early recognition and appropriate treatment are the keys to a successful outcome.

Background/objectives: Children with celiac disease (CD) are at risk for decreased bone mineral density (BMD) because of fat-soluble vitamin malabsorption, inflammation and/or under-nutrition. The study objective was to determine the interrelationships between vitamin K/D status and lifestyle variables on BMD in children and adolescents with CD at diagnosis and after 1 year on the gluten-free diet (GFD)., Subjects/methods: Children and adolescents aged 3-17 years with biopsy proven CD at diagnosis and after 1 year on the GFD were studied. BMD was measured using dual-energy X-ray absorptiometry. Relevant variables included: anthropometrics, vitamin D/K status, diet, physical activity and sunlight exposure., Results: Whole-body and lumbar-spine BMD-z scores were low (< or = -1) at diagnosis (10-20%) and after 1 year (30-32%) in the children, independent of symptoms. Whole-body BMD-z scores (-0.55±0.7 versus 0.72±1.5) and serum levels of 25(OH) vitamin D (90.3±24.8 versus 70.5±19.8 nmol/l) were significantly lower in older children (>10 years) when compared with younger children (< or =10 years) (P<0.001). Forty-three percent had suboptimal vitamin D status (25(OH)-vitamin D <75 nmol/l) at diagnosis; resolving in nearly half after 1 year on the GFD. Twenty-five percent had suboptimal vitamin K status at diagnosis; all resolved after 1 year., Conclusions: Children and adolescents with CD are at risk for suboptimal bone health at time of diagnosis and after 1 year on GFD; likely due in part to suboptimal vitamin D/K status. Therapeutic strategies aimed at optimizing vitamin K/D intake may contribute to improved BMD in children with CD.

Aim: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms., Methods: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years., Results: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died., Conclusion: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.

Purpose: The purpose of the present study was to evaluate the quality of life (QoL) of children with CD and of their parents and to compare it with that of children without CD and of their parents., Methods: A case-control study was conducted to evaluate the quality of life of children (5-12 years) with CD and one of their parents, compared to the QoL of children without CD (and their parents as their caregivers ). The QoL was assessed by applying the following questionnaires: AUQUEI (children) and WHOQOL-BREF (parents)., Results: QoL was evaluated in 33 children with CD, 63 children without CD, and of their respective parents as their parent caregivers (96 adults). QoL total scores were similar between the groups of children with and without CD. However, in the Leisure dimension, the scores of children with CD were significantly lower than those of the controls (P = 0.029). Similarly, when assessing the QoL of the parents, we found scores significantly lower in the social dimension (P = 0.0196) for parents of children with CD compared to parents of children without CD. Family income presented an impact on the QoL in adults, but did not affect children. In CD group, children of mothers who had lower educational levels presented better scores in the function dimension, regarding self-care and autonomy., Conclusions: There is an impairment of the QoL of children with CD and of their parents, with regard to social life, particularly in the leisure (children) and social (adults) dimensions.

Background: Alterations of small intestinal transit and gallbladder (GB) motility have been reported in celiac disease (CD) in studies involving, in most cases, non-physiological experimental conditions and artificial stimuli to motility. Our aims were to quantitate non-invasively small intestinal transit time and GB emptying during administration of a physiological and palatable solid meal, and to assess the effect of gluten-free diet (GFD)., Methods: We simultaneously measured mouth-to-cecum transit time (MCTT) using a validated H(2) breath test, and GB motility using ultrasonography. We studied CD patients before (n = 19) and during (n = 14) GFD, and healthy volunteers (n = 24) following administration of a physiological solid meal (Kcal 539)., Key Results: Mouth-to-cecum transit time was more prolonged in CD (mean ± SEM: 235 ± 96 min) than in controls (169 ± 65 min, P = 0.0039). The GB fasting volume and postprandial residual volume were significantly higher in CD than in controls, and GB emptying constant was slower in CD than in controls. During GFD, GB emptying reverted to normal, but MCTT remained unchanged (229 ± 69 min) and more prolonged in CD than in controls (P = 0.0139). During GFD, duodenal infiltration with lymphocytes and mast cells persisted higher than that in controls, and the number of mast cells lying in proximity of nervous endings did not change., Conclusions & Inferences: Slow postprandial MCTT in response to a physiological meal does not revert to normal during GFD, an effect mirroring incomplete histopathologic recovery., (© 2011 Blackwell Publishing Ltd.)

Background: Epithelial barrier defects are well known in coeliac disease, but the mechanisms are only poorly defined. It is unclear, whether barrier disturbance reflects upregulated epithelial transcytosis or paracellular leakage., Objective: To characterise the molecular structure and function of the epithelial tight junction (TJ) and mechanisms of its dysregulation., Methods: Molecular analysis of proteins involved in TJ assembly and their regulation was performed by western blotting and confocal microscopy correlated to electrophysiology., Results: A complex alteration of the composition of epithelial TJ proteins (with more pore-forming claudins like claudin-2 and a reduction in tightening claudins like claudin-3, -5 and -7) was found for protein expression and subcellular localisation, responsible for an increase in paracellular biotin-NHS uptake. In contrast, epithelial apoptosis was only moderately elevated (accounting for a minor portion of barrier defects) and epithelial gross lesions--for example, at cell extrusion zones, were absent. This TJ alteration was linked to an altered localisation/expression of proteins regulating TJ assembly, the polarity complex protein Par-3 and the serine-/threonine phosphatase PP-1., Conclusions: Changes in cell polarity proteins Par-3 and PP-1 are associated with altered expression and assembly of TJ proteins claudin-2, -3, -5 and -7 and ZO-1, causing paracellular leakage in active coeliac disease.

Gluten-sensitive enteropathy (GSE) is increasingly diagnosed in adults. The symptoms of this disease can overlap with those of functional dyspepsia. The prevalence of GSE in dyspepsia has been reported to be 1.2-6.2% and could be higher if the entire spectrum of lesions related to gluten sensitivity, including lymphocytic enteropathy, is considered. Patients with dyspepsia secondary to GSE could be mistakenly diagnosed with functional dyspepsia unless upper gastrointestinal endoscopy is completed with duodenal biopsy and immunostaining for intraepithelial lymphocytes. A missed diagnosis could have major consequences in terms of morbidity and mortality and quality of life. Consequently, endoscopic study of patients with dyspepsia should be completed by duodenal biopsy when there are symptoms suggestive of GSE., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

In genetically predisposed individuals, dietary gluten in wheat, rye and barley triggers celiac disease, a systemic autoimmune disorder hallmarked by an extensive small-bowel mucosal immune response. The current conception of celiac disease pathogenesis is that it involves components of both innate and adaptive immunity whose activation typically leads to small-bowel villous atrophy with crypt hyperplasia. Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet excluding all wheat-, rye- and barley-containing food products. During the diet, the clinical symptoms improve and the small-bowel mucosal damage recovers, while re-introduction of gluten into the diet leads to re-appearance of the symptoms and deterioration of the small-bowel mucosal architecture. In view of the restricted nature of the diet, alternative treatment is warranted. Improved understanding of the molecular basis of celiac disease has enabled researchers to suggest other therapeutic approaches. Although there is no animal model reproducing all features of celiac disease, the use of in vitro approaches including a variety of cell lines and the celiac patient small-bowel mucosal biopsy organ culture has generated knowledge about pathogenesis of celiac disease. In these culture systems, gluten induces different effects that can be quantified, thus also enabling studies concerning the efficacy of candidate therapeutic compounds for celiac disease. This review describes the intestinal epithelial cell models, celiac patient T-cell lines and clones, as well as the small-bowel mucosal organ culture methods widely used in studies of celiac disease, and summarizes the major findings obtained with these systems.

Background: HLA-DQB1*02 homozygosity was shown to be more common in patients with complicated rather than uncomplicated celiac disease (CD)., Goals: To study HLA-DQA1 and DQB1 profile in adult patients with different forms of CD, including patients with complicated and potential CD, the most affected and the most preserved histologic end of the pathologic celiac spectrum., Study: HLA-DQA1 and DQB1 molecular typing was performed in 218 adult CD patients (169 with uncomplicated CD, 27 with complicated CD, and 22 with potential CD) and 224 healthy stem cell donors. HLA-DQA1 and DQB1 gene polymorphism was analyzed using polymerase chain reaction sequence-specific primers and/or reverse polymerase chain reaction sequence-specific oligonucleotides techniques., Results: As expected, the frequency of HLA-DQB1*02 allele, DQB1*02 homozygosity, and DQB1*0302 gene were statistically different in the 4 groups. However, multivariate analysis demonstrated that patients with potential CD have a higher frequency of both HLA-DQB1*0302 and HLA-DQB1*0603 alleles and a reduced frequency of DQB1*02 homozygosity compared with patients with uncomplicated and complicated CD., Conclusions: The increased frequency of DQB1*0302 and the reduced frequency of DQB1*02 homozygosity in potential CD is consistent with the idea that different clinical/pathologic evolutions might be related to different immunogeneses. This could be clinically relevant in the future.

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

Celiac disease is a multi-systemic autoimmune disease of the small bowel induced by gluten in genetically predisposed subjects. Highly specific and gluten-dependent production of auto-antibodies targeting self-proteins of the transglutaminase family occurs in the intestinal mucosa. These anti-transglutaminase antibodies are found deposited in intestinal and extra-intestinal tissue where they might exert biological effects, together with the intestinal mucosal gliadin-specific T lymphocytes. We conducted a brief review on antitransglutaminase antibodies effects, discussing their roles in the pathogenesis of several clinical manifestations of celiac disease.

There are several different diseases in gastroenterology with an important role of immunological mechanisms in their pathogenesis. We know autoimmune diseases with immunological reactions against liver or pancreatic tissue. In addition there are diseases like chronic inflammatory bowel diseases representing inappropriate immunological reactions followed by inflammation and tissue destruction. The research of the last decade has contributed significantly to the understanding of the pathogenesis of diseases based on immunological mechanisms and consequently to the development of novel therapeutic strategies targeting molecules. Chronic inflammatory bowel diseases, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune pancreatitis, and celiac disease are the most important diseases with immunological pathogenesis in Gastroenterology. Especially in chronic inflammatory bowel diseases ulcerative colitis and Crohn's disease with immunosuppressive drugs and monoclonal antibodies new preparations are used in therapy. Autoimmune pancreatitis was characterized as an own entity in the last years. Therefore, this review will focus on these diseases.

Aim: We investigated whether treatment with gliadin induces a paracellular permeability defect that enhances bacterial translocation to mesenteric lymph nodes (MLN) via resident dendritic cells (DC) expressing TLR-2 or 4 in HCD4/HLA-DQ8 transgenic mice., Methods: HLA-DQ8 transgenic mice were sensitized and subsequently gavaged with gliadin, in the presence or absence of AT1001 (paracellular permeability inhibitor). Non-sensitized mice were gavaged with indomethacin (permeability inducer) or rice cereal. CD11c and CD103 (DC markers) and TLR-2 and 4 were investigated by immunostaining. Intestinal permeability was assessed by paracellular flux of (51)Cr-EDTA in Ussing chambers. Bacterial translocation to MLN was performed by plate counting on aerobic and anaerobic conditions., Results: In gliadin-treated mice, both (51)Cr-EDTA flux in jejunal mucosa and aerobic and anaerobic bacterial counts in MLN were increased (p < 0.05) compared to indomethacin-treated mice and controls. The inhibitor AT1001 normalized (51)Cr-EDTA flux, but had no effect on bacterial translocation in gliadin-treated mice. In addition, changes in mucosal DC marker distribution such as increased (p < 0.05) trans-epithelial CD103(+) cells and reduction (p < 0.05) of CD11c immunostaining were detected in gliadin-treated mice. Moreover, changes in DC markers and TLR-2 or 4 immunophenotypes were not associated., Conclusions: Pharmacological restoration of paracellular permeability was not sufficient to prevent bacterial translocation in gluten-sensitive mice. We hypothesize that transcellular mechanisms involving CD103(+)DC and CD11c(+)DC may explain in gluten-sensitive HCD4/HLA-DQ8 transgenic mice the sustained increased bacterial translocation observed in the absence of a significant inflammatory response.

Objective: To assess the association between seroconversion and catch-up growth during the first year of a gluten-free diet (GFD) program in children with celiac disease (CD)., Methods: All prepubertal and biopsy-proven children diagnosed with CD between January 1999 and August 2009 were included in a retrospective study (n=55). Growth parameters and celiac antibodies were documented before and after 6 (period 1) and 12 months (period 2) of GFD, respectively., Results: Mean height velocity-standard deviation score (SDS) was significantly higher in period 1 compared with that in period 2 (2.90 +/- 3.20 vs. 0.20 +/- 2.08, p<0.001) irrespective of the serology status, with marginal difference in mean weight-SDS gain (p=0.074). Mean levels of height velocity-SDS and the weight-SDS gain were similar in the seropositive and seronegative groups in both periods of the study. Mean height-SDS and weight-SDS levels after 6 months were higher than those in baseline levels, both in seropositive (-0.47 +/- 0.91 vs. -0.82 +/- 0.82, p<0.001 and -0.59 +/- 1.17 vs. -1.11 +/- 1.33, p<0.001, respectively) and seronegative patients (-1.02 +/- 1.14 vs. -1.50 +/- 1.12, p<0.001 and -1.19 +/- 1.27 vs. -1.45 +/- 1.40, p=0.048, respectively). These growth parameters were higher at the end compared with the beginning of period 2, but only in seropositive patients., Conclusions: The most remarkable catch-up growth in children with CD can be expected during the first 6 months of GFD, irrespective of the serology status.

Objectives: To determine whether the information on the gluten content of nonprescription drugs is readily available from the manufacturer/supplier, to identify how patients are directed on the product labeling to obtain answers to questions that they have about the nonprescription medication, and to determine the time needed to obtain information about the gluten content of the product when contacting manufacturers/suppliers., Design: Descriptive, exploratory, nonexperimental study., Setting: United States during July 2010., Participants: Manufacturers/suppliers of 41 nonprescription drug products., Intervention: The packaging of the products was reviewed for information on gluten content. The manufacturer/supplier listed on each product's packaging was contacted using the phone number provided and questioned about the gluten content of the product. A uniform script was used for the telephone inquiry. The responses provided and the duration of the phone calls were documented. The manufacturer's websites also were reviewed for pertinent information., Main Outcome Measures: Gluten status of products, time spent on phone to determine gluten status, and availability of online information regarding gluten status., Results: Information concerning the gluten content was not included on any of the products' packaging. The mean time required to receive a response was 6.2 minutes (median 5 minutes). A total of 15 products were reported to be gluten free; 13 products were not tested, but the manufacturer/supplier stated that they did not add gluten to the products; 9 products did not have any gluten added by the manufacturer/ supplier, but no guarantee was made that the raw ingredients were gluten free; 2 products contained gluten; and 2 products had no available gluten status information. Gluten information was found on product websites for a total of six products. Four of those six websites indicated gluten status that was different from the information provided via the telephone call with the manufacturer., Conclusion: Information concerning the gluten content of many nonprescription drugs is relatively easy for patients to obtain if the manufacturer/supplier is contacted. Although the time to obtain a response was quite short for many of the inquiries, it took a substantial amount of time to receive the requested information from some of the companies.

Many human genes have adapted to the constant threat of exposure to changing environmental conditions. Balancing selection is the result of an initial stage of positive selection that favors the spread in a population of a new allele until selection opposes its fixation and balanced situation is established. It is suggested that the disadvantageous celiac patients survived the last two millennias echo-catastrophes by adapting to the extreme temperature changes and their consequences in Europe. Genetic selective diversity induced by changing environment, enabled the celiac population to survive. Such a genetic positive selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci and the HLA celiac disease-associated repertoire, enabling the celiac to overcome iron deficiency anemia and micro pathogen richness, respectively. The increased incidence of those evolutionary events in the celiac patients is a recent phenomenon that occurred in the latest era of the modern human history. The present hypothesis can shed light on additional selective genetic adaptations, echo catastrophe-driven that are at the basis of autoimmune disease-affected population survival and current expansion., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases., Methods: Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses., Key Results: Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses., Conclusions & Inferences: Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin., (© 2011 Blackwell Publishing Ltd.)

With a prevalence of 1% in western populations, Celiac disease (CD) is one of the most common inflammatory disorders of the small intestine. CD is often assumed to have its onset in childhood, but it has recently been suggested that adults can also develop CD. Clinical manifestations vary according to age group: infants and young children present with diarrhea, abdominal distention, and failure to thrive, whereas adults that develop CD not only present with diarrhea, but also with silent manifestations such as anemia, osteoporosis, or neurological symptoms. In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. mmunohistochemistry of the small intestine of patients shows villous atrophy, crypt hyperplasia, and elevated levels of intraepithelial lymphocytes (IELs). The only therapy until now is a gluten-free diet, which will normalize the clinical and histological manifestations and allows the patients to live an otherwise normal life. part of the symptoms are oral manifestations as dental enamel defects, aphthous ulcers and Atrophic Glossitis. The prevalence of caries in CD patiens is law as compared to the healthy population and in some cases the normal eruption sequence of the teeth was damaged. Part of the undiagnosed CD patients are among our patients and the enamel defects they present are misdiagnosed as tetracycline pigmentation or white spot lesions it is the practitioners responsibility to add CD as a possible cause to the findings and refer the patient to further examination. The case report in this paper presents a 47 years old female patient who was a patient in my practice for 25 years. When she became 40 she was diagnosed as CD and treated accordingly over the years enamel defects were treated conservatively. As the lesions became more frequent and unpredictable the patient demanded a full mouth solution that would restore both the functional and esthetical problems she had with her dentition. A full Porcelane Fused to Metal (PFZ) crowns were fabricated and the patient got a solution to both here demands. The crowns used were 3M Lava zirconia crowns and the case is presented as step by step sequence.

Background: Celiac disease (CD) is an immunologic enteropathy triggered by the intake of gluten. It is thought that the enteropathy impairs gut function and absorption., Objective: We assessed the zinc-absorption capacity and small-bowel integrity in children with CD., Design: Children in whom a diagnosis of CD was considered clinically and either confirmed (n = 16; Marsh score ≥3) or not (n = 22; Marsh score of 0) with a small-bowel biopsy (SBB) were recruited. The fractional absorption of zinc (FAZ) was determined by the administration of an oral (67)Zn dose (2.5 mg) and an intravenous (70)Zn dose (0.2 mg) 2 h before and during the SBB, respectively. Spot urine samples were collected, and zinc isotopic ratios were determined by ion-coupled plasma mass spectrometry. Gut health was assessed by the ingestion of (13)C-sucrose (20 g) after an overnight fast, and breath samples were collected and analyzed by isotope ratio mass spectrometry., Results: There was no difference in FAZ between children with a Marsh score ≥3 (mean ± SEM: 0.68 ± 0.05) and children with a Marsh score of 0 (0.74 ± 0.05). The exchangeable zinc pool (EZP) was significantly (P < 0.05) lower in children with a Marsh score ≥3 (2.6 ± 0.8 mg/kg) than in children with a Marsh score of 0 (3.8 ± 1.4 mg/kg). Gut function in children with a Marsh score ≥3 (4.5 ± 0.7% cumulative dose recovered at 90 min) was lower than the lower cutoff of a normal gut-function breath test (5.06% cumulative dose recovered at 90 min) but not significantly different from that in children with a Marsh score of 0 (4.9 ± 0.4%). There was a significant (P < 0.01) correlation between zinc absorption and gut function in children with CD., Conclusions: Zinc absorption did not appear below usual amounts in subjects with CD. Children with CD have impaired gut function that may affect their zinc nutritional status as shown by a smaller EZP. However, the EZP decrease in children with CD was not compared with that in healthy control subjects, and its biological meaning is uncertain.

Untreated celiac disease is associated with lower bone mineral density (BMD), body weight and fat mass compared with controls. There are few longitudinal studies examining changes in body composition after celiac disease diagnosis. The aim of this study was to compare changes in BMD and body composition in celiac seropositive cases who had undergone baseline and follow-up dual energy x-ray absorptiometry (DXA) with seronegative controls. Celiac serologic and BMD databases for the Province of Manitoba, Canada, were linked. Endomysial antibody (EMA) seropositive cases and EMA seronegative controls over age 40 who had serologic testing within 6 months of DXA testing and a follow-up DXA were extracted from the databases. Changes in BMD, BMI and body composition were compared in the 2 groups. The 43 EMA seropositive cases had lower baseline spine and hip BMD, BMI and fat measurements compared with 233 EMA seronegative controls. For seropositive versus seronegative individuals there were greater increases in mean spine BMD (4.6%/year vs 0.7% spine, p < 0.0001), hip BMD (3.0 %/year vs 0.2%/year hip, p < 0.0001), and body weight (2.8%/year vs 0.3%/year, p < 0.0001). Increases in mean abdominal fat (2.4%/year vs 0.4%/year, p < 0.0001) were also greater in seropositive versus seronegative individuals, while increases in hip fat were less marked (0.9%/year vs 0.3%/year, p = 0.0071). This longitudinal database study documents significant improvements in BMD in seropositive cases. BMI and fat measures also increased, with the abdominal fat compartment demonstrating the greatest increase. Further studies are needed to determine the clinical significance of this regional increase in abdominal fat., (Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: An association between coeliac disease (CD) and functional gastrointestinal disorders (FGIDs) has at present only been demonstrated in adults., Aims: To assess the prevalence of FGIDs at 1 year and the role of psychological aspects on the development of FGIDs in CD children., Methods: One-hundred consecutive CD children (36M and 64F) were followed up for 1 year. Fifty-six children (25M and 31F) represented the control group. All children and/or their parents completed validated questionnaires for GI symptoms, depression, and anxiety. GI symptoms at diagnosis and after 1 year of gluten-free diet (GFD) were compared., Results: Twenty-three/82 (28%) CD patients followed up prospectively, on GFD from at least 1 year, fulfilled the Rome III criteria for FGIDs compared with 5/56 (8.9%) controls (P = 0.008; χ² = 6.8; OR: 3.97; 95% CI: 1.40-11.21). Children complaining with GI symptoms alone [21/52 (40.3%)] more likely fulfilled Rome III criteria for FGIDs after 1 year of GFD than children with extra-intestinal symptoms (P = 0.045). CD children with FGDIs presented significantly higher anxiety and depression compared to CD children without FGIDs and controls (P = 0.02)., Conclusions: This study demonstrates that children with CD on a GFD for a year have a much higher prevalence of functional GI symptoms than do controls. Whether the risk is due to the residua of a chronic inflammatory process, and/or due to psychological factors remains to be further tested., (© 2011 Blackwell Publishing Ltd.)

Unlabelled: Recent research data concerning the risk of coeliac disease confirm that introduction of food containing gluten during breast-feeding not later than 6 months of life is justified. According to ESPGHAN and EFSA introduction of solid foods in the diet of infants between 4-6 months of age is safe., Aim of Study: Evaluation of feeding practices in healthy full-term infants after implementation of the recommendations of coeliac disease prevention., Material and Methods: Conducted analysis concerned 54 healthy full-term infants, living in Warsaw, aged 6 to 12 months. Of these, 27 children were exclusively breastfed for the first 6 months of life and 27 children were non-breastfed. The differences between selected parameters of nutritional status and diets of breastfed and nonbreastfed infants were evaluated by using t-Student test. Relations between quantitative variables were assessed by chi2 test., Results: Products containing gluten were introduced into the breastfed children's diet in the 5th month of life in 22% of studied subgroup, in the 6th month - in 15%, in the 7th or 8th month - in 30%, between 9th and 11th month - in 22% and 11% of these children have not received food containing gluten in the first year of life. In the group of non-breastfed infants 15% received products with gluten before 5th month of life, 15% in 5th month, 11% at age of 6 months, 22% between 7th and 8th month, 15% in 11th month and 22% of children have not received food containing gluten in the first 12 months of life. An average daily intake of foods with varying content of gluten amounted to 55 g in breastfed infants and 70.5 g in non-breastfed infants (p <0.05)., Conclusions: In the pilot study it was found out that nutritional recommendations concerning prophylaxis of coeliac disease were not implemented correctly by the majority of mothers of studied infants. Products containing gluten were introduced to the infant's diet too early or too late and mostly in larger quantities than it was recommended. Due to the small number of studied children it is important to carry out the investigation on a larger sample. At the same time it is necessary to introduce more effective methods of implementing nutritional recommendations concerning prophylaxis of celiac disease.

Objective: We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet., Methods: The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity., Results: Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05)., Conclusions: Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.

Background: This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion., Design: Analysis of data derived from two separate data banks., Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25)., Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by (99 m)Tc-ECD SPECT. Statistical analysis was done through logistic regression., Results: MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group., Conclusion: In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

Malabsorption syndrome encompasses numerous clinical entities that result in chronic diarrhea, abdominal distention, and failure to thrive. These disorders may be congenital or acquired and include cystic fibrosis and Shwachman-Diamond syndrome; the rare congenital lactase deficiency; glucose-galactose malabsorption; sucrase-isomaltase deficiency; adult-type hypolactasia leading to acquired lactose intolerance. The pathology may be due to impairment in absorption or digestion of nutrients resulting in Nutritional deficiency, gastrointestinal symptoms, and extra gastrointestinal symptoms. Treatment is aimed at correcting the deficiencies and symptoms to improve quality of life. Common disorders of malabsorption celiac disease, pernicious anemia, and lactase deficiency are discussed in this article., (Copyright © 2011. Published by Elsevier Inc.)

Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated., (© 2011 Copyright the Author. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Genome-wide association studies are providing insight into the genetic basis of common complex diseases: more than 1150 genetic loci [2165 unique single nucleotide polymorphisms (SNPs)] have recently been associated to 159 complex diseases. The hunt for genes contributing to immune-related diseases has been particularly successful in celiac disease, for example, with 27 genome-wide significantly associated loci identified so far. One of the current challenges is how to move from a genetic association with a disease to finding disease-associated genes and causal variants, as a step towards understanding the underlying disease process. About 50% of disease-associated SNPs affect the expression of nearby genes (so-called expression quantitative traits loci or eQTLs) and these can provide clues for finding causal variants. Although eQTLs can be useful, fine mapping and sequencing are required to refine the association signal. Ultimately, sophisticated study designs will be needed to find the causal variants involved in complex diseases. In this review, we use celiac disease as an example to describe the different aspects that need to be considered on the path from genetic association to disease-causing variants., (2011 John Wiley & Sons A/S.)

Celiac disease affects approximately 1% of the U.S. population, and many cases go undiagnosed until later in life. A wide range of symptoms, illnesses, and disorders may accompany undiagnosed celiac disease. This article reviews screening, diagnosis, and treatment of celiac disease for the NP., (Copyright © 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.)

Aim: The coeliac disease deprives affected individual of the main nutritive factors, which are essential to promote body development: coeliac children are often subject to weight loss and have a lower somatic growth rate compared to healthy children. In addition, it is proven that prolonged malnutrition can have irreversible effects on dental eruption: teeth development also suffers a delay or it is slowed down in coeliac children. The purpose of this study was to evaluate and quantify the persistence of a delay in the dental age in children with coeliac disease and the presence of a possible constant relationship between the estimated delay in skeletal development and that referred to the dental age., Materials and Methods: Seventy children (24 males and 46 females) were selected, all affected by coeliac disease, aged between 5.3 and 13.8 years, with a mean age of 9 years +/- 22 months SD. Through teleradiography of the skull in latero-lateral projection and orthopantomography of the dental arches, the estimate of the skeletal development and dental age was carried out for each patient, applying two specific methods extensively described in the literature., Results and Conclusion: The results obtained, in agreement with the literature, show how the dental age, which is delayed in children affected by coeliac disease, may be considered as a reliable indicator of somatic growth and also of biological age. Furthermore, a gluten-free diet has considerable beneficial effects on skeletal development in relation to the dental age, in agreement with the hypothesis that dental development is controlled by different regulatory mechanisms, totally independent from those that influence skeletal development and the somatic and sexual development of the individual, even if the delay of dental development decreases progressively from the time of diagnosis of coeliac disease to introduction of a gluten-free diet.

In celiac disease, highly sensitive and specific serum endomysial and transglutaminase 2 antibody tests are widely used in identifying patients for diagnostic endoscopy and small-bowel biopsy. In addition, the recently developed deamidated gliadin peptide antibody tests show promise in celiac disease diagnostics. In view of these apparent problems attending the diagnostic gold standard, gluten-induced small-bowel mucosal villous atrophy with crypt hyperplasia, other diagnostic approaches beyond conventional histology have been introduced. Furthermore, the diagnostic criteria for celiac disease are currently under revision with an eye also to noninvasive diagnostic strategies.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It is one of the most common lifelong disorders on a worldwide basis. Celiac enteropathy is the final consequence of an abnormal immune reaction, showing features of both an innate and an adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extraintestinal features, and silent forms. The only available treatment consists in dietary exclusion of grains containing gluten. New pharmacological treatment are currently under scrutiny.