Recent PubMed Articles on Coeliac Disease (External)

Assessment of Machine Learning Detection of Environmental Enteropathy and Celiac Disease in Children.

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Assessment of Machine Learning Detection of Environmental Enteropathy and Celiac Disease in Children.

JAMA Netw Open. 2019 Jun 05;2(6):e195822

Authors: Syed S, Al-Boni M, Khan MN, Sadiq K, Iqbal NT, Moskaluk CA, Kelly P, Amadi B, Ali SA, Moore SR, Brown DE

Abstract
Importance: Duodenal biopsies from children with enteropathies associated with undernutrition, such as environmental enteropathy (EE) and celiac disease (CD), display significant histopathological overlap.
Objective: To develop a convolutional neural network (CNN) to enhance the detection of pathologic morphological features in diseased vs healthy duodenal tissue.
Design, Setting, and Participants: In this prospective diagnostic study, a CNN consisting of 4 convolutions, 1 fully connected layer, and 1 softmax layer was trained on duodenal biopsy images. Data were provided by 3 sites: Aga Khan University Hospital, Karachi, Pakistan; University Teaching Hospital, Lusaka, Zambia; and University of Virginia, Charlottesville. Duodenal biopsy slides from 102 children (10 with EE from Aga Khan University Hospital, 16 with EE from University Teaching Hospital, 34 with CD from University of Virginia, and 42 with no disease from University of Virginia) were converted into 3118 images. The CNN was designed and analyzed at the University of Virginia. The data were collected, prepared, and analyzed between November 2017 and February 2018.
Main Outcomes and Measures: Classification accuracy of the CNN per image and per case and incorrect classification rate identified by aggregated 10-fold cross-validation confusion/error matrices of CNN models.
Results: Overall, 102 children participated in this study, with a median (interquartile range) age of 31.0 (20.3-75.5) months and a roughly equal sex distribution, with 53 boys (51.9%). The model demonstrated 93.4% case-detection accuracy and had a false-negative rate of 2.4%. Confusion metrics indicated most incorrect classifications were between patients with CD and healthy patients. Feature map activations were visualized and learned distinctive patterns, including microlevel features in duodenal tissues, such as alterations in secretory cell populations.
Conclusions and Relevance: A machine learning-based histopathological analysis model demonstrating 93.4% classification accuracy was developed for identifying and differentiating between duodenal biopsies from children with EE and CD. The combination of the CNN with a deconvolutional network enabled feature recognition and highlighted secretory cells' role in the model's ability to differentiate between these histologically similar diseases.

PMID: 31199451 [PubMed - in process]

Celiac disease in Iranian irritable bowel syndrome patients; a systematic review and meta-analysis.

Celiac disease in Iranian irritable bowel syndrome patients; a systematic review and meta-analysis.

Gastroenterol Hepatol Bed Bench. 2019;12(2):85-97

Authors: Azami M, Badfar G, Abangah G, Mahmoudi L

Abstract
Aim: The present study was conducted to evaluate the prevalence, clinical symptoms and pathological findings of celiac disease (CD) in irritable bowel syndrome (IBS) patients in Iran.
Background: Several studies show high prevalence of CD in IBS patients, but the results are contradictory.
Methods: The present study was conducted based on MOOSE protocol and results were reported according to PRISMA guideline. The search was done using international online databases (Scopus, PubMed, Science Direct, Cochrane Library, Embase, and Web of Science), national databases and Google Scholar search engine.
Results: The pooled prevalence of CD in 2,367 Iranian IBS patients was estimated to be 6.13% (95%CI: 4.11-9.05). The prevalence of CD in men and women with IBS was 4.28% (95% CI: 2.45-7.37) and 7.19% (95% CI: 4.51-11.28), respectively. The serological prevalence of anti tTG-IgA (11 studies with 2901 IBS patients) and AGA-IgG (4 studies with 936 IBS patients) was estimated to be 5.35% (95%CI: 3.60-7.89) and 6.35% (95%CI: 2.05-18.03), respectively. The clinical symptoms of CD among IBS patients included predominant diarrhea (47.87% [95%CI: 22.46-74.43]), predominant constipation (17.34% [95%CI: 9.17-30.35]), and alternative diarrhea and constipation (27.84% [95%CI: 11.57-53.23]). According to pathological findings based on marsh classification, the prevalence of CD at stages 1, 2 and 3 were 30.89% (95%CI: 13.25-56.68), 36.56% (95%CI: 21.74-54.45) and 52.87% (95%CI: 14.48-88.13), respectively.
Conclusion: In the present meta-analysis, we observed a high prevalence for CD among Iranian IBS patients, which is higher than global estimates. Examination of all IBS patients in terms of CD seems to be necessary, but cost-effectiveness should be considered.

PMID: 31191832 [PubMed]

Celiac Disease in Asia.

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Celiac Disease in Asia.

Gastroenterol Clin North Am. 2019 03;48(1):101-113

Authors: Makharia GK, Catassi C

Abstract
Celiac disease, once thought to be very uncommon in Asia, is now emerging in many Asian countries. Although the absolute number of patients with celiac disease at present is not very high, this number is expected to increase markedly over the next few years/decades owing to increasing awareness. It is now that the medical community across the Asia should define the extent of the problem and prepare to handle the impending epidemic of celiac disease in Asia.

PMID: 30711203 [PubMed - indexed for MEDLINE]

Epidemiology of Celiac Disease.

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Epidemiology of Celiac Disease.

Gastroenterol Clin North Am. 2019 03;48(1):1-18

Authors: Ludvigsson JF, Murray JA

Abstract
Celiac disease is a common, chronic inflammatory disorder of the small intestine triggered by exposure to gluten in individuals with certain genetic types. This disorder affects people of any age or gender. Although often thought to be European in origin, it is now global in extent. Presentations are variable, from asymptomatic patients to severe malnutrition. Initial detection usually relies on celiac-specific serology, and confirmation often requires intestinal biopsy. There have been substantial increases in prevalence and incidence over the last 2 decades for reasons that are almost certainly environmental but for which there is no clarity as to cause.

PMID: 30711202 [PubMed - indexed for MEDLINE]

Onset of menarche is not delayed in Slovenian patients with celiac disease.

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Onset of menarche is not delayed in Slovenian patients with celiac disease.

J Int Med Res. 2019 Feb;47(2):815-822

Authors: Mičetić-Turk D, Vlaisavljević V, Turk E, Pogačar MŠ

Abstract
OBJECTIVE: Celiac disease (CD) is an autoimmune disorder associated with numerous health problems, including reproductive disorders. This study was performed to analyze the association between CD and the menstrual cycle in a group of patients with CD and compare these patients' characteristics with those of healthy women.
METHODS: The study included 145 patients with CD (age, 15-51 years) and 162 healthy women (age, 18-55 years). Age at menarche and characteristics of the menstrual cycle were obtained by an anonymous questionnaire developed for the study.
RESULTS: The age at onset of menarche was 12 to 14 years in 72.9% of the patients with CD and 77.3% of the healthy controls. For most patients (74.2%), the length of the menstrual cycle was around 27 to 28 days with 4 to 5 days of bleeding. Furthermore, 8.4% of patients versus 5.9% of controls experienced bleeding between cycles.
CONCLUSIONS: Our results suggest that in Slovenia, the age at menarche in patients with CD is 12.7 years, which is comparable with that in healthy women. We conclude that CD (treated or untreated) may not be associated with late menarche.

PMID: 30477370 [PubMed - indexed for MEDLINE]

Mitochondrial neurogastrointestinal encephalomyopathy imitating Crohn's disease: a rare cause of malnutrition.

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Mitochondrial neurogastrointestinal encephalomyopathy imitating Crohn's disease: a rare cause of malnutrition.

J Gastrointestin Liver Dis. 2018 Sep;27(3):321-325

Authors: Kučerová L, Dolina J, Dastych M, Bartušek D, Honzík T, Mazanec J, Kunovský L

Abstract
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by a mutation in the TYMP gene encoding thymidine phosphorylase. MNGIE causes gastrointestinal and neurological symptoms in homozygous individuals and is often misdiagnosed as anorexia nervosa, inflammatory bowel disease, or celiac disease. We present the case of a 26-year-old female with MNGIE, who was initially diagnosed with anorexia nervosa and Crohn's disease. The diagnosis of MNGIE was established by biochemical confirmation of elevated serum and urine thymidine and deoxyuridine levels after multiple examinations and several years of disease progression and ineffective treatment. Subsequent molecular genetic testing demonstrated a homozygous TYMP gene mutation. MNGIE should be considered in patients with unexplained malnutrition, intestinal dysmotility, and atypical neurological symptoms.

PMID: 30240477 [PubMed - indexed for MEDLINE]

HLA-DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies.

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HLA-DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies.

Int J Immunogenet. 2019 Jun 11;:

Authors: Poddighe D, Capittini C, Gaviglio I, Brambilla I, Marseglia GL

Abstract
Through a retrospective analysis of a real-life cohort of children with celiac disease (CD), who underwent HLA-DQ genotyping, we supported our previous findings indicating the presence of HLA-DQB1*02 allele in at least 90%-95% of pediatric patients. In the present study, reporting the HLA-DQ analysis from 184 children (age range: 1-16 years) diagnosed with CD in a single centre, we found that 97.29% of all these CD children (n = 179 out of 184 genotyped patients) resulted to be carriers of at least one copy of HLA-DQB1*02 allele. If a widened screening for CD should result to be appropriate in the pediatric population after further clinical research, this observation might be potentially exploited to consider a two-step screening strategy, starting with the HLA-DQB1*02 targeted analysis followed by the specific serology for CD in these predisposed patients only. However, additional and larger studies are needed to support our findings.

PMID: 31187602 [PubMed - as supplied by publisher]

Interpretation and implementation of the revised European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on pediatric celiac disease amongst consultant general pediatricians in Southwest of England.

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Interpretation and implementation of the revised European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on pediatric celiac disease amongst consultant general pediatricians in Southwest of England.

Indian J Gastroenterol. 2019 Jun 10;:

Authors: Paul SP, Adams HL, Basude D, Collaborators

Abstract
BACKGROUND: Celiac disease (CD) is a lifelong condition with significant morbidity and requires an accurate diagnosis. Guidelines for pediatric CD were revised by the European and British Societies of Paediatric Gastroenterology Hepatology and Nutrition in 2012 and 2013, respectively. New recommendations introduced non-biopsy pathway (NBP) of diagnosis for a selective group of symptomatic children whose anti-tissue transglutaminase (anti-tTG) antibody titer is greater than ten times upper limit of normal. A clear understanding of the guidelines amongst consultant pediatricians will ensure all children with suspected CD receive a prompt and secure diagnosis. The aim of this study was to establish the interpretation and implementation of the revised guideline for CD amongst consultant general pediatricians in Southwest England (SWE) during the study period.
METHODS: Telephone/email survey was conducted amongst consultant general pediatricians (n ≈ 140) working in 12 secondary care hospitals across SWE. The survey included eight questions incorporating three main themes: understanding of diagnostic pathway particularly for non-biopsy diagnosis, awareness of laboratory tests involved, and variations in practice in relation to the revised guidelines.
RESULTS: Responses were available from 101/140 (72%). One hundred respondents were aware of the revised guidelines for diagnosing CD. However, only 17 respondents stated all the criteria of the guideline required for diagnosis by NBP, with further 17 seeking immediate advice from a specialist. Forty-four listed both the criteria for HLA-DQ2/DQ8 testing applicable to pediatricians. Forty-nine out of 100 pediatricians would commence gluten-free diet only after all the results were available. Thirty-three pediatricians also considered asymptomatic children with high anti-tTG titer eligible for diagnosis of CD by NBP.
CONCLUSIONS: There is a need for improved understanding of revised CD guidelines amongst consultant general pediatricians especially while using the NBP and requesting HLA-DQ2/DQ8 testing.

PMID: 31183842 [PubMed - as supplied by publisher]

Serological screening for coeliac disease in patients with juvenile idiopathic arthritis.

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Serological screening for coeliac disease in patients with juvenile idiopathic arthritis.

Arab J Gastroenterol. 2019 Jun 07;:

Authors: Sahin Y, Sahin S, Barut K, Cokugras FC, Erkan T, Adrovic A, Kutlu T, Kasapcopur O

Abstract
BACKGROUND AND STUDY AIMS: Juvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA).
PATIENTS AND METHODS: This prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA.
RESULTS: Of the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs.
CONCLUSION: We did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.

PMID: 31182344 [PubMed - as supplied by publisher]

Rate, Risk Factors and Outcomes of Non-adherence in Pediatric Patients with Celiac Disease: a Systematic Review.

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Rate, Risk Factors and Outcomes of Non-adherence in Pediatric Patients with Celiac Disease: a Systematic Review.

Clin Gastroenterol Hepatol. 2019 Jun 04;:

Authors: Myléus A, Reilly NR, Green PHR

Abstract
BACKGROUND AND AIMS: The only treatment for celiac disease is strict adherence to a gluten-free diet (GFD). We performed a systematic review to investigate the rate of adherence to a GFD in children with celiac disease, risk factors that affect adherence, and outcomes of non-adherence.
METHODS: We searched PubMed, Cochrane Library, EBSCO, and Scopus for studies through January 2019. We included observational studies of ≥50 children diagnosed with celiac disease and recommended for placement on a GFD. We collected data on adherence assessment (self-report, serology tests, structured dietary interview, biopsies, or assays for gluten immunogenic peptides), risk factors, and outcomes related to adherence. Findings were presented with medians, range, and a narrative synthesis.
RESULTS: We identified 703 studies; of these, 167 were eligible for full-text assessment and 49 were included in the final analysis, comprising 7850 children. Rates of adherence to a GFD ranged from 23% to 98%. Comparable rates (median rates of adherence, 75%-87%) were found irrespective of how assessments were performed. Adolescents were at risk of non-adherence and children whose parents had good knowledge about celiac disease adhered more strictly. Non-adherence associated with patient growth, symptoms, and quality of life.
CONCLUSION: In a systematic review of 49 studies of children with celiac disease, we found substantial variation in adherence to a GFD among patients. Rate of adherence was not associated with method of adherence measurement, so all methods appear to be useful, with lack of consensus on the ideal metric. Studies are needed to determine the best method to ensure adherence and effects on long-term health.

PMID: 31173891 [PubMed - as supplied by publisher]

ASSOCIATION OF TNF- α-308G>A POLYMORPHISM WITH SUSCEPTIBILITY TO CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

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ASSOCIATION OF TNF- α-308G>A POLYMORPHISM WITH SUSCEPTIBILITY TO CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Arq Gastroenterol. 2019 May 20;56(1):88-94

Authors: Aflatoonian M, Moghimi M, Akbarian-Bafghi MJ, Morovati-Sharifabad M, Jarahzadeh MH, Neamatzadeh H

Abstract
BACKGROUND: There is increasing evidence to show that TNF-α -308G>A polymorphism may be a risk factor for celiac disease, but the results are inconsistent.
OBJECTIVE: Thus, we aimed to perform a meta-analysis involving published studies up to January 2019 to elucidate the association.
METHODS: To assess the effect of TNF-α -308G>A polymorphism on celiac disease susceptibility, we searched PubMed, ISI Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI) databases to identify eligible studies, without restriction. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to celiac disease.
RESULTS: A total of 11 studies with 1147 cases and 1774 controls were selected for this meta-analysis. The pooled results indicated that TNF-α -308G>A polymorphism was associated with increased risk of celiac disease (A vs G: OR=2.077, 95% CI=1.468-2.939, P=≤0.001; AA vs GG: OR=8.512, 95% CI=3.740-19.373, P=≤0.001; AA+AG vs GG: OR=1.869, 95% CI=1.161-3.008, P=0.010; and AA+AG vs GG: OR=4.773, 95% CI=3.181-7.162, P≤0.001). Subgroup analysis by ethnicity also revealed significant association in Caucasians. In addition, there was a significant association between TNF-α -308G>A polymorphism and celiac disease risk in Italy, Spain and PCR-FRLP group studies.
CONCLUSION: Our meta-analysis suggests that the TNF-α -308G>A polymorphism plays an important role in celiac disease susceptibility. However, our results are still needed to strengthen by further studies in different ethnicities and larger sample sizes.

PMID: 31141070 [PubMed - in process]

Faecal Scent as a Novel Non-Invasive Biomarker to Discriminate between Coeliac Disease and Refractory Coeliac Disease: A Proof of Principle Study.

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Faecal Scent as a Novel Non-Invasive Biomarker to Discriminate between Coeliac Disease and Refractory Coeliac Disease: A Proof of Principle Study.

Biosensors (Basel). 2019 May 27;9(2):

Authors: Rouvroye MD, Wicaksono A, Bosch S, Savelkoul E, Covington JA, Beaumont H, Mulder CJ, Bouma G, de Meij TGJ, de Boer NKH

Abstract
Currently, the gold standard for diagnosis of coeliac disease (CD) is based on serology and gastroduodenoscopy with histology of duodenal mucosal biopsies. The aim of this study was to evaluate the potential of faecal volatile organic compounds (VOCs) analysis as a novel, non-invasive tool to discriminate between CD in remission in patients on a gluten-free diet (GFD), refractory coeliac disease (RCD) and controls without CD. Patients with an established diagnosis of CD on a GFD, RCD and healthy controls (HC) were instructed to collect a faecal sample. All subjects completed questionnaires on clinical symptoms, lifestyle and dietary information. Faecal VOCs were measured using gas chromatography-ion mobility spectrometry. A total of 13 CD, 7 RCD and 10 HC were included. A significant difference in VOC profiles between CD and RCD patients (area under the curve (AUC) ± 95% CI: 0.91 (0.79-1) p = 0.000) and between CD and HC (AUC ± 95% CI: 0.71 (0.51-0.91) p = 0.0254) was observed. We found no significant differences between faecal VOC patterns of HC and RCD. Based on faecal VOCs, CD could be discriminated from RCD and HC. This implies that faecal VOC analysis may hold potential as a novel non-invasive biomarker for RCD. Future studies should encompass a larger cohort to further investigate and validate this prior to application in clinical practice.

PMID: 31137798 [PubMed - in process]

Rhabdomyolysis and coeliac disease: A causal or casual association? A case report and review of literature.

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Rhabdomyolysis and coeliac disease: A causal or casual association? A case report and review of literature.

Clin Res Hepatol Gastroenterol. 2018 02;42(1):e7-e13

Authors: Mandato C, Rossi A, Caldore M, Lamba M, Rocco M, Auricchio R, Vajro P, Siani P

Abstract
BACKGROUND: Rhabdomyolysis is a rare, potentially life-threatening condition, caused by multiple disorders. The association with Coeliac Disease (CD) has been rarely reported and in these cases muscular damage was imputed to hypokalemia. Herein we describe a new case of severe rhabdomyolysis in a child subsequently diagnosed as affected by CD, and review previous reports.
CASE PRESENTATION: A 3-year-old boy was referred for diarrhea, brown urine, muscular pain/weakness, and no history of muscular trauma. At entry, laboratory tests showed elevated levels of creatine kinase (CK) (x100 unv) and aspartate aminotransferase (AST) (x10 unv), alanine aminotrasferase (ALT) (x5 unv); electrolytes were within the reference range. Twenty-four hours after admission serum CK peaked 115,000 U/L and transaminases increased up to 30 times unv. Hyperhydration treatment was started with renal function monitoring. Urine output decreased little, while serum creatinine and urea nitrogen stayed within the reference range. Serum potassium levels went down to 2.8 mEq/L at day 3, in spite of supplementation. The patient completely recovered at day 16. Main metabolic causes of rhabdomyolysis were ruled out by appropriate tests. Because of rarely reported cases of CD/rhabdomyolysis, anti-tissue transglutaminase (tTG) antibodies were measured and found positive (IgA 34 U/mL, unv <9). HLA typing was DQA1 05:02, DQB1 03:02. As jejunal biopsy showed patchy villous atrophy, gluten free diet (GFD) was prescribed. One year after starting GFD, histology was normal.
REVIEW OF LITERATURE: Literature (search engines: PUB MED and GOOGLE SCHOLAR) from 1980 to 2016 retrieved 8 cases (age range: 12 to 75 years old) previously described.
CONCLUSION: The present case suggests to check for CD in children with severe rhabdomyolysis. Because severe rhabdomyolysis itself may elevate the serum potassium levels, hypokalemia might go unrecognized as the cause of muscular damage.

PMID: 28606713 [PubMed - indexed for MEDLINE]

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

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Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

J Clin Immunol. 2019 May 25;:

Authors: Lougaris V, Sorlini A, Monfredini C, Ingrasciotta G, Caravaggio A, Lorenzini T, Baronio M, Cattalini M, Meini A, Ruggeri L, Salpietro A, Pilotta A, Grazzani L, Prandi E, Felappi B, Gualdi G, Fabiano A, Fuoti M, Ravelli A, Villanacci V, Soresina A, Badolato R, Plebani A

Abstract
PURPOSE: Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce.
METHODS: We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up.
RESULTS: Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID).
CONCLUSIONS: In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

PMID: 31129864 [PubMed - as supplied by publisher]

Reproductive complications in celiac disease patients in Slovenia.

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Reproductive complications in celiac disease patients in Slovenia.

Eur J Obstet Gynecol Reprod Biol. 2019 May 15;238:90-94

Authors: Pogačar MŠ, Vlaisavljević V, Turk E, Mičetić-Turk D

Abstract
OBJECTIVE: Celiac disease is associated with higher risk of infertility, recurrent abortions, and adverse outcomes in pregnancy and in puerperium. The aim of the study was to analyse the association between celiac disease and reproductive disorders in the group of celiac patients and compare these to healthy controls.
METHODS: A retrospective case-control matched study. The association between celiac disease and menstrual cycle, gyneco-obstetrical complications was assessed with a questionnaire specifically developed for the study. 144 celiac women and 61 celiac men, members of Slovenian Celiac Society, together with 71 healthy women and 31 healthy men participated in the study.
RESULTS: A higher percentage of celiac women (27.1%) had difficulties in conception of the first child when compared to healthy controls (12.7%) (p = 0.042). In addition, celiac women experienced more complications than healthy controls during the pregnancy, such as abortions or intrauterine growth retardation (p < 0.005). In our study, the prevalence of reproductive problems was not the same in celiac males and females. Altogether 2 celiac men (3.3%) reported having fertility problems, however, the difference between male cases and controls was not statistically significant (p = 0.548).
CONCLUSION: Physicians should examine women with unexplained infertility, recurrent abortions or intrauterine growth retardation for undiagnosed celiac disease. Compared with healthy women, women with celiac disease have increased risk of spontaneous abortions, preterm delivery and fewer successful pregnancies.

PMID: 31125708 [PubMed - as supplied by publisher]

Vitamin A levels are comparable between children with newly diagnosed celiac disease and non-celiac controls.

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Vitamin A levels are comparable between children with newly diagnosed celiac disease and non-celiac controls.

Acta Paediatr. 2019 May 24;:

Authors: Weintraub Y, Ben-Tov A, Dotan G, Yerushalmy-Feler A, Weiner D, Levy D, Lubetzky R, Cohen S

Abstract
AIM: Nutritional deficiencies associated with celiac disease include iron, folic acid, and fat soluble vitamins. This study compared the prevalence and degree of vitamin A deficiency among newly diagnosed celiac disease patients to controls in a developed country.
METHODS: This prospective cohort study included all children evaluated by gastroscopy at Dana-Dwek Children's Hospital, Israel, between September 2014 to February 2017. Vitamin A, haemoglobin, C-reactive protein (CRP), ferritin, tissue-transglutaminase, immunoglobulin A and vitamin D levels were measured.
RESULTS: Of the 113 children (69% females), 47 were diagnosed with celiac disease whereas the others were the controls (mean age of 8.2 ± 3.8 years and 12.4 ± 3.5 years, respectively). There was no group difference in vitamin A, vitamin D or CRP levels. Among celiac children two had true vitamin A deficiency compared with three controls while 18 celiac children had subclinical vitamin A deficiency compared with 25 controls (p >0.05).
CONCLUSION: Paediatric celiac disease was not associated with increased prevalence of vitamin A deficiency. Children evaluated for gastrointestinal complaints in a developed country were found to have an unexpectedly high prevalence of subclinical vitamin A deficiency. Further prevalence and causality assessments of vitamin A deficiency in developed countries are needed. This article is protected by copyright. All rights reserved.

PMID: 31124160 [PubMed - as supplied by publisher]

Constitutive alterations in vesicular trafficking increase the sensitivity of cells from celiac disease patients to gliadin.

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Constitutive alterations in vesicular trafficking increase the sensitivity of cells from celiac disease patients to gliadin.

Commun Biol. 2019;2:190

Authors: Lania G, Nanayakkara M, Maglio M, Auricchio R, Porpora M, Conte M, De Matteis MA, Rizzo R, Luini A, Discepolo V, Troncone R, Auricchio S, Barone MV

Abstract
Celiac Disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. Some gliadin peptides (e.g., A-gliadin P57-68) induce an adaptive Th1 pro-inflammatory response. Other gliadin peptides (e.g., A-gliadin P31-43) induce a stress/innate immune response involving interleukin 15 (IL15) and interferon α (IFN-α). In the present study, we describe a stressed/inflamed celiac cellular phenotype in enterocytes and fibroblasts probably due to an alteration in the early-recycling endosomal system. Celiac cells are more sensitive to the gliadin peptide P31-43 and IL15 than controls. This phenotype is reproduced in control cells by inducing a delay in early vesicular trafficking. This constitutive lesion might mediate the stress/innate immune response to gliadin, which can be one of the triggers of the gliadin-specific T-cell response.

PMID: 31123714 [PubMed]

Gut microbiome structure and metabolic activity in inflammatory bowel disease.

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Gut microbiome structure and metabolic activity in inflammatory bowel disease.

Nat Microbiol. 2019 02;4(2):293-305

Authors: Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ, Sauk JS, Wilson RG, Stevens BW, Scott JM, Pierce K, Deik AA, Bullock K, Imhann F, Porter JA, Zhernakova A, Fu J, Weersma RK, Wijmenga C, Clish CB, Vlamakis H, Huttenhower C, Xavier RJ

Abstract
The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.

PMID: 30531976 [PubMed - indexed for MEDLINE]

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