Recent PubMed Articles on Coeliac Disease (External)

Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity.

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Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity.

JAMA Pediatr. 2017 Oct 09;:

Authors: Kemppainen KM, Vehik K, Lynch KF, Larsson HE, Canepa RJ, Simell V, Koletzko S, Liu E, Simell OG, Toppari J, Ziegler AG, Rewers MJ, Lernmark Å, Hagopian WA, She JX, Akolkar B, Schatz DA, Atkinson MA, Blaser MJ, Krischer JP, Hyöty H, Agardh D, Triplett EW, Environmental Determinants of Diabetes in the Young (TEDDY) Study Group

Abstract
Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.
Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD.
Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D.
Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.
Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity.
Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02).
Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.

PMID: 29052687 [PubMed - as supplied by publisher]

Feasibility of screening for T1D and celiac disease in a pediatric clinic setting.

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Feasibility of screening for T1D and celiac disease in a pediatric clinic setting.

Pediatr Diabetes. 2016 Sep;17(6):441-8

Authors: Gesualdo PD, Bautista KA, Waugh KC, Yu L, Norris JM, Rewers MJ, Baxter J

Abstract
OBJECTIVE: Type 1 diabetes (T1D) or celiac disease (CD) develops in at least 2% of the general population. Early detection of disease-specific autoimmunity and subsequent monitoring would be possible if screening tests were more widely available. Currently, screening for islet autoimmunity is available only in a research setting, and CD-specific autoimmunity screening is limited to those in high-risk groups. This study assessed the feasibility of incorporating T1D and CD autoantibody screening into a pediatric practice.
METHODS: Patient engagement strategies, blood collection preference, blood sample volume, rate of autoantibody detection in the general population, and parental satisfaction were assessed. Over 5 weeks, research staff recruited 200 patients, aged 2-6 yr from two pediatric practices in the Denver area to be screened for islet autoantibodies (IAs) and the transglutaminase antibody.
RESULTS: Of the 765 parents approached, 200 (26%) completed the same-day screening. Of the 565 subjects who did not complete the screening, 345 expressed interest, but were unable to make a participation decision. A finger stick, compared with a venous draw, was the preferred method of sample collection. Both methods yielded sufficient blood volume for autoantibody determination. IAs or the transglutaminase antibody were detected in 11 subjects. Parents expressed satisfaction with all aspects of participation.
CONCLUSIONS: The results of this study suggest that it is feasible to conduct this type of screening in a pediatric clinic. Such screening could lead to increased disease awareness and the possible benefits that can result from early detection.

PMID: 26251221 [PubMed - indexed for MEDLINE]

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

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Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

Gastroenterology. 2017 Oct;153(4):924-935

Authors: Werkstetter KJ, Korponay-Szabó IR, Popp A, Villanacci V, Salemme M, Heilig G, Lillevang ST, Mearin ML, Ribes-Koninckx C, Thomas A, Troncone R, Filipiak B, Mäki M, Gyimesi J, Najafi M, Dolinšek J, Dydensborg Sander S, Auricchio R, Papadopoulou A, Vécsei A, Szitanyi P, Donat E, Nenna R, Alliet P, Penagini F, Garnier-Lengliné H, Castillejo G, Kurppa K, Shamir R, Hauer AC, Smets F, Corujeira S, van Winckel M, Buderus S, Chong S, Husby S, Koletzko S, ProCeDE study group

Abstract
BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach.
METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified.
RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00).
CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

PMID: 28624578 [PubMed - indexed for MEDLINE]

Detecting celiac disease in patients with Down syndrome.

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Detecting celiac disease in patients with Down syndrome.

Am J Med Genet A. 2016 Dec;170(12):3098-3105

Authors: Sharr C, Lavigne J, Elsharkawi IM, Ozonoff A, Baumer N, Brasington C, Cannon S, Crissman B, Davidson E, Florez JC, Kishnani P, Lombardo A, Lyerly J, McDonough ME, Schwartz A, Berrier KL, Sparks S, Stock-Guild K, Toler TL, Vellody K, Voelz L, Skotko BG

Abstract
The main purposes of this undertaking were to determine how often patients with Down syndrome (DS) are screened for celiac disease (CD) across five DS specialty clinics, which symptoms of CD are most often reported to DS specialty providers at these clinics, and, how many individuals were diagnosed with CD by these clinics. This was accomplished by following 663 individuals with DS for 1 year, across five clinics in different states specializing in the comprehensive care of people with DS. Of the 663 participants, 114 individuals were screened for CD at their visit to a DS specialty clinic. Protracted constipation (43.2%) and refractory behavioral problems (23.7%) were symptoms most often reported to DS specialty providers. During the 1 year study period, 13 patients screened positive for CD by serology. Of those, eight underwent duodenal biopsy, and three were diagnosed with CD. We conclude that CD is an important consideration in the comprehensive care of individuals with DS. However, while symptoms are common, diagnoses are infrequent in DS specialty clinics. © 2016 Wiley Periodicals, Inc.

PMID: 27605215 [PubMed - indexed for MEDLINE]

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases.

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Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases.

United European Gastroenterol J. 2017 Oct;5(6):819-826

Authors: Valle J, Morgado JMT, Ruiz-Martín J, Guardiola A, Lopes-Nogueras M, García-Vela A, Martín-Sacristán B, Sánchez-Muñoz L

Abstract
BACKGROUND: Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs.
OBJECTIVE: The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases.
METHODS: A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs.
RESULTS: In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting.
CONCLUSION: Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.

PMID: 29026596 [PubMed]

The DMT1 IVS4+44C>A polymorphism and the risk of iron deficiency anemia in children with celiac disease.

The DMT1 IVS4+44C>A polymorphism and the risk of iron deficiency anemia in children with celiac disease.

PLoS One. 2017;12(10):e0185822

Authors: Tolone C, Bellini G, Punzo F, Papparella A, Miele E, Vitale A, Nobili B, Strisciuglio C, Rossi F

Abstract
BACKGROUND: Iron deficiency anemia in celiac disease is related to impaired duodenal mucosal uptake, due to villous atrophy. Iron enters the enterocytes through an apical divalent metal transporter, DMT1. Different DMT1 transcripts have been identified, depending on the presence of an iron-responsive element that allows DMT1 up-regulation during iron starvation. An intronic DMT1 polymorphism, IVS4+44C>A, has been associated with metal toxicity, and the CC-carriers show high iron levels.
AIMS: This study investigates the association between DMT1 IVS4+44C>A and anemia in a cohort of 387 Italian celiac children, and the functional role of the polymorphism.
METHODS AND RESULTS: By association analysis, we found that DMT1 IVS4+44-AA genotype confers a four-fold risk of developing anemia, despite of atrophy degree. By analysis of mRNA from gastroesophageal biopsies, we found that total DMT1 is significantly upregulated in presence of mild, but not severe, atrophy, independently from IVS4+44C>A variant, and in normal but not in atrophic CC-biopsies. Moreover, we found that A-allele is associated to preferential expression of the DMT1 transcripts lacking the iron-responsive element, thus limiting the DMT1 overexpression that normally occurs to respond to iron starvation.
DISCUSSION: Possibly, the IVS4+44-AA-related dysregulation of the iron-induced changes in DMT1 expression is not able to impair iron absorption in physiological condition. However, if exacerbated by the concomitant massive loss of functional absorbing tissue paralleling worsened stages of villus atrophy, it might be ineffective in counteracting iron deficiency, despite of DMT1 overexpression.
CONCLUSION: We suggest, for the first time, that celiac disease may unmask the contribution of the DMT1 IVS4+44C>A polymorphism to the risk of anemia.

PMID: 29023457 [PubMed - in process]

Coeliac disease: to biopsy or not?

Coeliac disease: to biopsy or not?

Nat Rev Gastroenterol Hepatol. 2017 Oct 11;:

Authors: Reilly NR, Husby S, Sanders DS, Green PHR

Abstract
Coeliac disease is increasingly recognized as a global problem in both children and adults. Traditionally, the findings of characteristic changes of villous atrophy and increased intraepithelial lymphocytosis identified in duodenal biopsy samples taken during upper gastrointestinal endoscopy have been required for diagnosis. Although biopsies remain advised as necessary for the diagnosis of coeliac disease in adults, European guidelines for children provide a biopsy-sparing diagnostic pathway. This approach has been enabled by the high specificity and sensitivity of serological testing. However, these guidelines are not universally accepted. In this Perspective, we discuss the pros and cons of a biopsy-avoiding pathway for the diagnosis of coeliac disease, especially in this current era of the call for more biopsies, even from the duodenal bulb, in the diagnosis of coeliac disease. In addition, a contrast between paediatric and adult guidelines is presented.

PMID: 29018278 [PubMed - as supplied by publisher]

Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity.

Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity.

Pediatrics. 2017 Oct 10;:

Authors: Hagopian W, Lee HS, Liu E, Rewers M, She JX, Ziegler AG, Lernmark Å, Toppari J, Rich SS, Krischer JP, Erlich H, Akolkar B, Agardh D, TEDDY Study Group

Abstract
BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.
METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.
RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors.
CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.

PMID: 29018046 [PubMed - as supplied by publisher]

Faltering Growth – recognition and management

Faltering Growth – recognition and management

Book. 2017 09

Authors: National Guideline Alliance (UK)

Abstract
The term 'faltering growth' (previously called ‘failure to thrive’) is widely used to refer to a slower rate of weight gain in childhood than expected for age and sex. The term faltering growth is preferred as periods of slow growth may represent temporary variation from the expected pattern and the word ‘failure’ may be seen as pejorative. Various definitions of faltering growth have been used in the past, meaning estimates of prevalence in the UK vary widely. The World Health Organization (WHO) has produced growth standards, based on longitudinal studies of healthy breastfed infants. These standards, along with UK term and preterm infant growth data, have been incorporated into UK WHO growth charts for monitoring growth in UK children. A child’s weight, length or height and head circumference can be plotted on these charts to provide a visual representation of growth over time. Epidemiological data suggest that healthy children usually progress relatively consistently along a growth centile. New-born infants normally lose weight in the first days of life. Persisting or large weight losses can cause concern in parents, carers and health professionals about ineffective establishment of feeding. In older children, faltering growth can occur when nutritional intake does not meet a child's specific energy requirements. Undernutrition presents as a relatively slow weight gain, demonstrated by a fall across weight centiles on the growth chart. Children with faltering growth may be identified by routine growth monitoring or by parental or health professional concern. Standard management is usually community based, with support and advice provided to increase energy intake and manage challenging feeding behaviour. Some children will be referred to paediatric dietitians or paediatricians for further assessment and management. Certain health conditions predispose children to faltering growth (for example, cystic fibrosis or coeliac disease). Specific treatment for these conditions can improve or restore expected rates of weight gain. In children with no specific cause for faltering growth, simple interventions to increase nutritional intake may be effective in improving weight gain. Faltering growth in early childhood may be associated with persisting problems with appetite and feeding. The cause of faltering growth in the absence of a specific underlying health condition is likely to be complex and multifactorial. In the past, child neglect or socioeconomic and educational disadvantage were often considered to be likely contributors. While neglected children may be undernourished, neglect is an uncommon explanation for faltering growth. Similarly, significant associations with socioeconomic or educational factors have not been demonstrated. There is variation across the UK in care provided for infants, children and families where concerns are raised about early weight loss or faltering growth. There is cultural and socioeconomic variation in starting and continuing breastfeeding, the approach to introducing complementary solid food and choice of foods, feeding behaviour and parental acceptance of feeding support and advice.


PMID: 28991420

Corrigendum: Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

Corrigendum: Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

Front Cell Infect Microbiol. 2017;7:427

Authors: Lucero Y, Oyarzún A, O'Ryan M, Quera R, Espinosa N, Valenzuela R, Simian D, Alcalde E, Arce C, Farfán MJ, Vergara AF, Gajardo I, Mendez J, Carrasco J, Errázuriz G, González M, Ossa JC, Maiza E, Perez-Bravo F, Castro M, Araya M

Abstract
[This corrects the article on p. 376 in vol. 7, PMID: 28879170.].

PMID: 28983475 [PubMed - in process]

Evidence Supporting Serology Based Pathway for Diagnosing Coeliac Disease In Asymptomatic Children From High-Risk Groups.

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Evidence Supporting Serology Based Pathway for Diagnosing Coeliac Disease In Asymptomatic Children From High-Risk Groups.

J Pediatr Gastroenterol Nutr. 2017 Sep 27;:

Authors: Paul SP, Sandhu BK, Spray CH, Basude D, Ramani P

Abstract
OBJECTIVE: The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing coeliac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titre of greater than 10-times upper limit of normal (>10xULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. Aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups.
METHODS: From March 2007 - February 2017 prospective data on anti-tTG titre, age, sex and reason for screening was collected at diagnostic endoscopy on all asymptomatic children being diagnosed with CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titres was analysed.
RESULTS: 157 asymptomatic children were diagnosed with CD. 84/157 (53.5%) had antitTG >10xULN (normal <10 IU/ml) and 75/84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. 53/84 children had anti-tTG >200IU/ml and total villous atrophy was present in 29/53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around £1275/child in the United Kingdom.
CONCLUSION: All 75 asymptomatic children from high-risk groups with anti-tTG >10xULN had histology proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.

PMID: 28957985 [PubMed - as supplied by publisher]

Association of autoimmune thyroiditis and celiac disease with Juvenile Polyposis due to 10q23.1q23.31 deletion: Potential role of PI3K/Akt pathway dysregulation.

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Association of autoimmune thyroiditis and celiac disease with Juvenile Polyposis due to 10q23.1q23.31 deletion: Potential role of PI3K/Akt pathway dysregulation.

Eur J Med Genet. 2017 Jul;60(7):380-384

Authors: Guaraldi F, Di Nardo G, Tarani L, Bertelli L, Susca FC, Bagnulo R, Resta N

Abstract
Juvenile Polyposis (JP) is a rare hereditary condition characterized by diffuse hamartomatous gastrointestinal polyposis, associated with a significantly increased risk of neoplastic transformation. Most of the cases are caused by SMAD and BMPR1A mutations, while 10q23 microdeletions, encompassing both PTEN and BMPR1A oncogenes, are extremely rare, typically associated with more aggressive JP, and extraintestinal features overlapping with PTEN Hamartoma Tumor Syndrome. We present the first case of a young female with multiple autoimmune disorders (i.e. thyroiditis and celiac disease), associated with JP, cardiac defects and epilepsy, who carries a de novo heterozygous 10q23.1q23.31 deletion. The dysregulation of the PI3K/Akt pathway is advanced as the putative mechanism connecting autoimmune, malformative and neoplastic disorders. A literature review of clinical manifestation, gene alterations and the treatment of patients with 10q23 deletion is also provided, highlighting the importance of comprehensive, long-term, multi-disciplinary management, aimed at early identification and treatment of both intestinal and extraintestinal disorders.

PMID: 28434922 [PubMed - indexed for MEDLINE]

Iron Status in Pediatric Celiac Disease: A Retrospective Chart Review.

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Iron Status in Pediatric Celiac Disease: A Retrospective Chart Review.

J Pediatr Gastroenterol Nutr. 2017 Sep 26;:

Authors: Popov J, Baldawi M, Mbuagbaw L, Gould M, Mileski H, Brill H, Pai N

Abstract
This study assessed the role of serum ferritin as a non-invasive biomarker in the diagnosis and monitoring of pediatric celiac disease. A retrospective chart review was performed on patients < 18 years old at time of diagnosis (n = 193) between 1998-2015. 653 paired values demonstrated a weak negative correlation between serum ferritin and TTG-IgA (r = -0.114; p = 0.004), necessitating further evaluation. A significant relationship was found between reduction of TTG-IgA and increase in serum ferritin after institution of a gluten-free diet (p < 0.0001), suggesting that resolution of villous damage is necessary for promoting adequate iron absorption.

PMID: 28953524 [PubMed - as supplied by publisher]

Efficacy of a point-of-care test based on deamidated gliadin peptides for the detection of celiac disease in pediatric patients.

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Efficacy of a point-of-care test based on deamidated gliadin peptides for the detection of celiac disease in pediatric patients.

Rev Esp Enferm Dig. 2017 Sep 27;109:

Authors: Polanco I, Koester Weber T, Martínez-Ojinaga E, Molina M, Sarria J

Abstract
OBJECTIVE: The objective of the study was to assess the effectiveness of a point-of-care test (POCT) based on deamidated gliadin peptides (DGP) compared to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria diagnosis in the early detection of celiac disease (CD) in pediatric patients.
METHODS: One hundred children (≤ 18 years) with suspected CD were selected, including siblings of celiac children that underwent gastroscopy for other gastrointestinal conditions. Patients with severe disease, following a gluten-free diet (GFD), with gastrointestinal bleeding, coagulopathy and infections in the last month were excluded. All children were evaluated with a POCT that detects immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to DGP and total IgA. The POCT results were compared to CD diagnosis according to current ESPGHAN criteria. This involved the detection of IgA tissue transglutaminase (tTG) antibodies, the results of an intestinal biopsy and genetic testing.
RESULTS: The prevalence of CD found in the present study was 48% (95% confidence interval in parenthesis 37.9-58.2%). The results of the POCT were concordant with the CD diagnosis made according to ESPGHAN criteria: 95.8% (85.7-99.4%) sensitivity, 98.1% (89.7-99.7%) specificity, 97.9% (88.7-99.6%) positive predictive value and 96.2% (87.0-99.4%) negative predictive value. Positive and negative likelihood ratios were 49.8 (7.2-347.5) and 0.04 (0.01-0.17), respectively. The POCT showed a 100% diagnostic accuracy in children younger than ten years of age. In total, three discordant results were found.
CONCLUSION: Due to the high diagnostic accuracy in the pediatric population, the POCT can be considered as an effective tool for the early diagnosis of CD, especially in patients younger than ten years of age.

PMID: 28950706 [PubMed - as supplied by publisher]

HMGB1 as a new biomarker of celiac disease in children: A multicenter study.

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HMGB1 as a new biomarker of celiac disease in children: A multicenter study.

Nutrition. 2017 May;37:18-21

Authors: Manti S, Cuppari C, Tardino L, Parisi G, Spina M, Salpietro C, Leonardi S

Abstract
OBJECTIVE: Despite the availability of specific sierology and point-of-care tests, the phenotypic heterogeneity and the symptoms fluctuation as well as the "open-window" existing among the late and silent forms cause often a delayed celiac disease (CD) diagnosis. Recently, it has been reported that high mobility group box 1 (HMGB1) mediates inflammation and gastrointestinal barrier failure. The aim of this study was to detect serum HMGB1 levels at CD diagnosis and to evaluate the relationship between serum HMGB1 levels and clinical and histologic phenotypes.
METHODS: 49 CD children and 44 healthy children were enrolled. Specific antitissue transglutaminase type 2, antideaminated form of gliadin antibodies, serum HMGB1 levels, and typical histopathological changes in duodenal mucosa were performed in all patients. Mucosal lesions were classified according to Marsh classification. In relation to clinical presentation, we classified patients into: typical, atypical and silent forms.
RESULTS: Serum HMGB1 levels were significantly higher in those with CD than those in the healthy control group (P < 0.001). Significant differences in serum HMGB1 levels were detected in children with typical CD form compared to both children with atypical CD form (P < 0.001) and children with silent CD form (P < 0.001). By using the Marsh classification, significant differences were found between subjects with grade 3 B-B1 and 3 C-B2 and villous atrophy, respectively (P < 0.05). On the contrary, no significant differences in serum HMGB1 levels in subgroups of children with grade 3 A compared to grade 3 B-B1 were detected.
CONCLUSIONS: HMGB1 is upregulated at diagnosis in all CD children, especially in typical form, and reflecting the histologic severity of disease.

PMID: 28359357 [PubMed - indexed for MEDLINE]

Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.

Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.

PLoS One. 2017;12(9):e0185025

Authors: Pietz G, De R, Hedberg M, Sjöberg V, Sandström O, Hernell O, Hammarström S, Hammarström ML

Abstract
BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.
METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.
RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.
CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

PMID: 28934294 [PubMed - in process]

Re-challenge Studies in Non-celiac Gluten Sensitivity: A Systematic Review and Meta-Analysis.

Related Articles

Re-challenge Studies in Non-celiac Gluten Sensitivity: A Systematic Review and Meta-Analysis.

Front Physiol. 2017;8:621

Authors: Lionetti E, Pulvirenti A, Vallorani M, Catassi G, Verma AK, Gatti S, Catassi C

Abstract
Background: Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by intestinal and/or extra-intestinal symptoms related to the ingestion of gluten in individuals that are not affected by either celiac disease (CD) or wheat allergy (WA). Since we do not have specific biomarkers for NCGS, the diagnosis is based on the evidence of a clear relationship between the ingestion of gluten (re-challenge) and clinical symptoms, after a remission during the gluten-free diet (GFD). Several re-challenge studies have been published so far to evaluate the real prevalence of NCGS, reporting conflicting results. In the present article, we provide a systematic review with meta-analysis of the existing literature on re-challenge studies to evaluate prevalence figures of NCGS after re-challenge procedures. Methods: All clinical trials performing a gluten re-challenge with or without a placebo control in patients with a suspected diagnosis of NCGS were included. Search results were limited to studies published in English language. No publication date or publication status restrictions were imposed. Results: Eleven studies were included in the meta-analysis. There was a considerable heterogeneity related to different sample size, type, and amount of gluten administered, duration of challenge and different type of placebo. The overall pooled percentage of patients with a diagnosis of NCGS relapsing after a gluten challenge was 30%, ranging between 7 and 77%. The meta-analysis showed a not significant relative risk (RR) of relapse after gluten challenge as compared to placebo (RR = 0.4; 95% CI = -0.15-0.9; p = 0.16). The overall pooled percentage of patients with a diagnosis of NCGS relapsing after a gluten challenge performed according to the recent Salerno criteria was significantly higher as compared to the percentage of patients relapsing after placebo (40 vs. 24%; p = 0.003), with a significant RR of relapse after gluten challenge as compared to placebo (RR = 2.8; 95% CI = 1.5-5.5; p = 0.002). Conclusions: The prevalence of NCGS after gluten re-challenge is low, and the percentage of relapse after a gluten or a placebo challenge is similar. However, a higher number of patients will be correctly classified with NCGS if applying the recent Salerno criteria.

PMID: 28928668 [PubMed]

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