Recent PubMed Articles on Coeliac Disease (External)

Structural variation in the gut microbiome associates with host health.

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Structural variation in the gut microbiome associates with host health.

Nature. 2019 04;568(7750):43-48

Authors: Zeevi D, Korem T, Godneva A, Bar N, Kurilshikov A, Lotan-Pompan M, Weinberger A, Fu J, Wijmenga C, Zhernakova A, Segal E

Abstract
Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to replicate in different cohorts. SVs are enriched for CRISPR-associated and antibiotic-producing functions and depleted from housekeeping genes, suggesting that they have a role in microbial adaptation. We find multiple associations between SVs and host disease risk factors, many of which replicate in an independent cohort. Exploring genes that are clustered in the same SV, we uncover several possible mechanistic links between the microbiome and its host, including a region in Anaerostipes hadrus that encodes a composite inositol catabolism-butyrate biosynthesis pathway, the presence of which is associated with lower host metabolic disease risk. Overall, our results uncover a nascent layer of variability in the microbiome that is associated with microbial adaptation and host health.

PMID: 30918406 [PubMed - indexed for MEDLINE]

Ribes orientale: A novel therapeutic approach targeting rheumatoid arthritis with reference to pro-inflammatory cytokines, inflammatory enzymes and anti-inflammatory cytokines.

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Ribes orientale: A novel therapeutic approach targeting rheumatoid arthritis with reference to pro-inflammatory cytokines, inflammatory enzymes and anti-inflammatory cytokines.

J Ethnopharmacol. 2019 Jun 12;237:92-107

Authors: Uttra AM, Alamgeer, Shahzad M, Shabbir A, Jahan S, Bukhari IA, Assiri AM

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Ribes orientale (Family Grossulariaceae) have long been used as a folk remedy to treat rheumatism and joints pain in Northern Areas of Pakistan.
AIM OF THE STUDY: The purpose of study was to observe the preventive efficacy of roots of Ribes orientale (RO) aqueous ethanolic extract (30:70) and its aqueous and n-butanol fractions in treating rheumatoid arthritis and to determine its possible mechanism of action.
MATERIAL AND METHODS: Arthritis was evaluated in vitro using heat induced bovine serum albumin and egg albumin denaturation and membrane stabilizing assays at 50-6400 μg/ml concentration of extract/fractions whereas, in vivo arthritis was evaluated at 50, 100, 200 mg/kg doses of extract/fractions in formaldehyde model by measuring rat paw volume/diameter. Moreover, highest effective dose (200 mg/kg) of extract/fractions was evaluated in Freünd complete adjuvant (FCA) model. Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. RO extract/fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) whereas, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Furthermore, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. The anti-oxidant activity of plant extract and fractions was evaluated using DPPH and reducing power assays. In addition, phytochemistry, total phenolic and flavonoid contents, and HPLC analysis of most active fraction (aqueous fraction) were performed.
RESULTS: Results showed that RO extract and fractions (notably aqueous fraction) significantly reduced protein denaturation and protected erythrocyte membrane in concentration dependent manner. Similarly, extract/fractions induced dose-dependent decrease in paw volume/diameter in the formaldehyde model. Plant extract and fractions significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, RO extract/fractions downregulated gene expression levels of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α whereas, upregulated those of IL-4 and IL-10, compared with FCA control rats. The radiographic and histopathologic improvement in joint architecture was also observed in RO treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of flavonoids and polyphenols.
CONCLUSION: Results indicated that suppression of pro-inflammatory enzymes/cytokines, inhibition of protein denaturation, lysosomal membrane stabilizing abilities, and redox/free radical scavenging properties of RO extract and fractions support anti-arthritic and immunomodulatory property of Ribes orientale that might be due to its polyphenolic and flavonoid constituents. This suggests that Ribes orientale roots may be used as a therapeutic agent for treating human arthritis.

PMID: 30872172 [PubMed - indexed for MEDLINE]

The Association of Inflammatory Bowel Diseases with Autoimmune Disorders: A Report from the epi-IIRN.

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The Association of Inflammatory Bowel Diseases with Autoimmune Disorders: A Report from the epi-IIRN.

J Crohns Colitis. 2019 Mar 26;13(3):324-329

Authors: Bar Yehuda S, Axlerod R, Toker O, Zigman N, Goren I, Mourad V, Lederman N, Cohen N, Matz E, Dushnitzky D, Gavish M, Borovsky N, Schwarts D, Dotan I, Turner D

Abstract
BACKGROUND AND AIMS: There are conflicting data on the association between inflammatory bowel diseases [IBD] and autoimmunity disorders. The aim of this study was to explore this association including the effect of medications.
METHODS: We utilized health administrative data collected by three of the four health maintenance organizations [HMOs] in Israel, covering 52% of the country's population. We explored the prevalence of the following autoimmune disorders: insulin-dependent diabetes mellitus [IDDM], psoriasis, Sjögren syndrome, coeliac disease, systemic lupus erythematosus [SLE], primary sclerosis cholangitis [PSC] and autoimmune thyroiditis, among all IBD patients vs non-IBD controls. Case ascertainment was determined according to validated computerized algorithms.
RESULTS: In total, 12625 IBD patients were compared to 12625 controls. A total of 1395 [11.1%] IBD patients had at least one autoimmune disease compared with 740 [5.9%] of non-IBD controls (odds ratio [OR] = 1.99 [95% confidence interval 1.81-2.19]; p < 0.05); all autoimmune diseases, except for thyroiditis, were more prevalent among IBD patients. Adjusted for confounding variables, anti-tumour necrosis factor [anti-TNF] medications were associated with a higher prevalence of psoriasis (54 [5.7%] in IBD vs 177 [4.1%] in controls; OR = 1.50 [1.07-2.08]; p < 0.05) but lower prevalence of Sjögren (1 [0.1%] vs 39 [0.9%]; OR [95% CI] = 0.13 [0.02-0.94]; p < 0.05) and coeliac disease (11 [1.2%] vs 68 [1.6%]; OR [95% CI] = 0.51 [0.27-0.99]; p < 0.05). Thiopurines and 5-aminosalicylates were not associated with any autoimmune disorder.
CONCLUSION: IBD is associated with all autoimmune diseases explored here except for thyroiditis. Anti-TNF users have a higher prevalence of psoriasis, and lower prevalence of Sjögren and coeliac disease.

PMID: 30304371 [PubMed - indexed for MEDLINE]

Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses.

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Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses.

Am J Trop Med Hyg. 2018 06;98(6):1577-1584

Authors: Syed S, Yeruva S, Herrmann J, Sailer A, Sadiq K, Iqbal N, Kabir F, Ahmed K, Qureshi S, Moore SR, Turner J, Ali SA

Abstract
Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children.

PMID: 29611507 [PubMed - indexed for MEDLINE]

Autoimmunity Predisposition in Girls With Turner Syndrome.

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Autoimmunity Predisposition in Girls With Turner Syndrome.

Front Endocrinol (Lausanne). 2019;10:511

Authors: Wegiel M, Antosz A, Gieburowska J, Szeliga K, Hankus M, Grzybowska-Chlebowczyk U, Wiecek S, Malecka-Tendera E, Gawlik A

Abstract
Background: Turner Syndrome is associated with an increased risk of autoimmune diseases, such as autoimmune thyroiditis, coeliac disease, type 1 diabetes mellitus, inflammatory bowel disease, alopecia areata, or vitiligo. The presence of isochromosome iXq and exposure to estradiol may contribute to the development of the autoimmune process. The aim of this study was to determine the prevalence of autoimmune diseases in a group of TS patients and to assess the impact of karyotype and puberty on the development of autoimmune diseases. Patients and Methods: The analysis encompassed clinical and biochemical data of 134 patients treated between 2001 and 2018. All the patients were examined for autoimmune disease symptoms and tested for the presence of antithyroperoxidase (anti-TPO) and antithyreoglobulin (anti-TG) antibodies. In 73 of the patients, anti-transglutaminase (anti-tTG) antibodies were measured. Thyroid function was assessed by measuring TSH and fT4 levels. Results: The mean follow-up was 5.7 ± 3 years. An autoimmune disease was diagnosed in 46 (34.3%) patients: 39 (29.1%) had only one disorder, whilst 7 (5.2%) presented two disorders. The most common disorder, observed in 40 (29.9%) patients, was thyroid autoimmunity. Hashimoto disease was diagnosed in 20 (14.9%) patients. Of the 73 patients tested for coeliac disease, 4 (5.5%) had anti-tTG and 2 (2.7%) presented overt coeliac disease. Vitiligo was diagnosed in 3 (2.2%) patients, type 1 diabetes mellitus or psoriasis were diagnosed in 2 (1.5%) patients, whilst alopecia areata or lichen sclerosus were diagnosed in 1 (0.7%) patient. The impact of karyotype or estradiol exposure on developing autoimmune diseases were not statistically significant. Conclusions: Our study showed a higher incidence of autoimmune diseases in TS, which is in line with the literature; however, the impact of iXq, or spontaneous/inducted puberty was not confirmed.

PMID: 31417494 [PubMed]

Robot-assisted radical prostatectomy due to a primary carcinoid prostatic tumour in a three-year-old child: a case report.

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Robot-assisted radical prostatectomy due to a primary carcinoid prostatic tumour in a three-year-old child: a case report.

Urology. 2019 Aug 12;:

Authors: Llorens de Knecht E, Guadarrama Vega S, Donate G, Palou Redorta J, Bujons Tur A

Abstract
We present an extremely rare case of a 3-year-old child with a primary carcinoid tumour of the prostate. A 3-year-old boy presented with failure to thrive, constipation, recurrent respiratory tract infections and pain in the genital area. His karyotype was normal and cystic fibrosis and coeliac disease were excluded prior to further investigation. An abdominopelvic CT scan revealed a prostatic mass. Transrectal ultrasound-guided prostate biopsy was therefore performed and pathological examination revealed a carcinoid tumour. A robotic radical prostatectomy was performed. As this is an innovative surgical approach, we describe the surgical technique used.

PMID: 31415779 [PubMed - as supplied by publisher]

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk.

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk.

JAMA. 2019 Aug 13;322(6):514-523

Authors: Andrén Aronsson C, Lee HS, Hård Af Segerstad EM, Uusitalo U, Yang J, Koletzko S, Liu E, Kurppa K, Bingley PJ, Toppari J, Ziegler AG, She JX, Hagopian WA, Rewers M, Akolkar B, Krischer JP, Virtanen SM, Norris JM, Agardh D, TEDDY Study Group

Abstract
Importance: High gluten intake during childhood may confer risk of celiac disease.
Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children.
Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017.
Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years.
Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels.
Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]).
Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

PMID: 31408136 [PubMed - in process]

Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome.

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Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome.

Nat Commun. 2019 Aug 09;10(1):3621

Authors: Russell JT, Roesch LFW, Ördberg M, Ilonen J, Atkinson MA, Schatz DA, Triplett EW, Ludvigsson J

Abstract
Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by far the greatest risk factors in the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on disease. Here, using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Both the core microbiome and beta diversity differ with HLA risk group and genotype. In addition, protective HLA haplotypes are associated with bacterial genera Intestinibacter and Romboutsia. Thus, general population cohorts are valuable in identifying potential environmental triggers or protective factors for autoimmune diseases that may otherwise be masked by strong genetic control.

PMID: 31399563 [PubMed - in process]

Evans Syndrome in Childhood: Long Term Follow-Up and the Evolution in Primary Immunodeficiency or Rheumatological Disease.

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Evans Syndrome in Childhood: Long Term Follow-Up and the Evolution in Primary Immunodeficiency or Rheumatological Disease.

Front Pediatr. 2019;7:304

Authors: Rivalta B, Zama D, Pancaldi G, Facchini E, Cantarini ME, Miniaci A, Prete A, Pession A

Abstract
Evans syndrome (ES) is a rare but challenging condition, characterized by recurrent and refractory cytopenia episodes. Recent discoveries highlighted that an appropriate diagnostic workup is fundamental to identify an underlying immune dysregulation such as primary immunodeficiencies or a rheumatological disease. We hereby describe clinical features and laboratory results of 12 pediatric patients affected by ES referred to the Pediatric Onco-Hematology Unit of Bologna. Patients experienced a median of four acute episodes of cytopenia with 9 years as median age at the onset of symptoms. In 8/12 (67%) patients an underlying etiology, primary immunodeficiencies, or rheumatological disease was identified. In 4/12 children, other immune manifestations were associated (Thyroiditis, Celiac disease, Psoriasis, Vitiligo, Myositis, Membranoproliferative Glomerulonephritis). ES remained the primary diagnosis in four patients (33%). At a median follow-up time of 4 years, 5/12 (42%) patients revealed a chronic ITP, partially responsive to second line therapy. Immunoglobulin Replacement Therapy (IRT) was effective with a good hematological values control in three patients with a secondary ES (ALPS, CVID, and a patient with Rubinstein Taybi Syndrome and a progressive severe B cell deficiency with hypogammaglobulinemia). Our experience highlights that, in pediatric patients, ES is often only the first manifestation of an immunological or rheumatological disease, especially when cytopenias are persistent or resistant to therapy, with an early-onset or when are associated with lymphadenopathy.

PMID: 31396497 [PubMed]

Adherence to the Gluten-free Diet and Health-related Quality of Life in an Ethnically Diverse Pediatric Population With Celiac Disease.

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Adherence to the Gluten-free Diet and Health-related Quality of Life in an Ethnically Diverse Pediatric Population With Celiac Disease.

J Pediatr Gastroenterol Nutr. 2018 Jun;66(6):941-948

Authors: Mager DR, Marcon M, Brill H, Liu A, Radmanovich K, Mileski H, Nasser R, Alzaben A, Carroll MW, Yap J, Persad R, Turner JM

Abstract
OBJECTIVES: Celiac disease (CD) is an autoimmune disease that requires lifelong adherence to a gluten-free diet (GFD). Adherence to the GFD in childhood may be poor and adversely influence health-related quality of life (HRQOL). The study purpose was to determine sociodemographic and socioeconomic factors influencing adherence to the GFD and HRQOL in a multiethnic cohort of youth with CD.
METHODS: A multisite (Edmonton, Hamilton, Toronto) study examining child-parent HRQOL in youth with CD (n = 243) and/or mild gastrointestinal complaints (GI-CON; n = 148) was conducted. Sociodemographic (age, child-parental age/education/ethnicity/place of birth), anthropometric (weight, height, body mass index), disease (diagnosis, age at diagnosis, duration, Marsh score, serology), household characteristics (income, family size, region, number of children/total household size), HRQOL (Peds TM/KINDL and Celiac Disease DUX), GI Complaints (PedsQL: Gastrointestinal Symptom Scale) and gluten intake were measured.
RESULTS: Younger age (<10 years), non-Caucasian ethnicity (parent/child), and presence of GI symptoms were associated with the highest rates of adherence to the GFD in CD children (P < 0.05). CD children (parent/child) had higher HRQOL (average, composite domains) than GI-CON (P < 0.05), but CD children were comparable to healthy children. Lack of GI symptoms, non-Caucasian ethnicity and age (<10 years) were associated with increased HRQOL in composite/average domains for CD (P < 0.05).
CONCLUSIONS: Child-parent perceptions of HRQOL in a multiethnic population with CD are comparable to healthy reference populations, but significantly higher than in parent/child GI-CON. Adherence to the GFD in ethnically diverse youth with CD was related to GI symptoms, age of the child, and ethnicity of the parent-child.

PMID: 29287009 [PubMed - indexed for MEDLINE]

Coeliac disease in children: the need to improve awareness in resource-limited settings.

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Coeliac disease in children: the need to improve awareness in resource-limited settings.

Sudan J Paediatr. 2019;19(1):6-13

Authors: Paul SP, Stanton LK, Adams HL, Basude D

Abstract
Coeliac disease (CD) is an immune-mediated systemic disorder caused by the ingestion of gluten. In children, it may present with intestinal or extra-intestinal manifestations such as diarrhoea, weight loss, iron deficiency anaemia or faltering growth. Diagnosis is confirmed by small bowel biopsies showing histological changes consistent with enteropathy. In 2012, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition revised the CD guidelines and suggested that, in a selective group of symptomatic children, CD can be diagnosed without the need for small-bowel biopsies. Management of CD is through strict adherence to a life-long gluten-free diet (GFD). CD is of great public health significance as its prevalence in developing countries has been found to be similar to that in developed countries. Early recognition and treatment improves prognosis. Patients and families require long term support to enable effective adherence to a GFD lifestyle. This alone can be challenging, but through support of health professionals and dietitians, can improve patient outcomes. In resource-limited settings medical professionals need to be creative in formulating cheaper and locally sourced gluten free options in close cooperation with the dietitians thereby ensuring availability of gluten free food items at affordable prices. In this paper, we gave an overview of the subject followed by authors' view to emphasize the need for improved awareness in resource-limited settings.

PMID: 31384082 [PubMed]

Misuse of serological screening tests for celiac disease in children: A prospective study in Italy.

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Misuse of serological screening tests for celiac disease in children: A prospective study in Italy.

Dig Liver Dis. 2019 Aug 02;:

Authors: Franceschini E, Lionetti ME, D'Adamo G, D'Angelo E, Gatti S, Naspi Catassi G, Malamisura B, Catassi C

Abstract
BACKGROUND: Despite a well-established diagnostic algorithm for celiac disease, it remains unclear whether prescriptions for celiac serological tests comply with the current pediatric guidelines.
AIM: To analyze the appropriateness of test prescription in children investigated for celiac disease in Italy, compared to the current European pediatric guidelines.
METHODS: All children who had performed a first evaluation for celiac disease were prospectively enrolled. Prescribed tests and related indications for testing were recorded, and compared to the European pediatric guidelines.
RESULTS: Overall, 202 children were enrolled (females 59%, mean age 7.1 years ±4.1) in two centers. The reasons for celiac disease testing were typical, atypical symptoms or celiac disease-associated conditions in 46.5%, 49%, and 4.5% of cases, respectively. First-line tests were IgA and IgG anti-transglutaminase antibodies in 88.1% and 29.7% of children, IgA and IgG anti-deamidated gliadin peptide antibodies in 43% and 47%, IgA and IgG anti native gliadin in 15.8%, IgA anti-endomysium antibodies in 44.5%, HLA predisposing genes in 10% of patients. Test redundancy was very common, and the current diagnostic guidelines were correctly followed only in 23/202 patients (11.4%).
CONCLUSIONS: Diagnostic European guidelines for celiac disease screening are often disregarded in Italy. Intervention to implement adherence to these guidelines is needed, with the aim of improving resource utilization, and quality of patient care.

PMID: 31383458 [PubMed - as supplied by publisher]

Early Probiotic Supplementation and the Risk of Celiac Disease in Children at Genetic Risk.

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Early Probiotic Supplementation and the Risk of Celiac Disease in Children at Genetic Risk.

Nutrients. 2019 Aug 02;11(8):

Authors: Uusitalo U, Andren Aronsson C, Liu X, Kurppa K, Yang J, Liu E, Skidmore J, Winkler C, Rewers MJ, Hagopian WA, She JX, Toppari J, Ziegler AG, Akolkar B, Norris JM, Virtanen SM, Krischer JP, Agardh D, TEDDY Study Group

Abstract
Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk.

PMID: 31382440 [PubMed - in process]

Structural insights on P31-43, a gliadin peptide able to promote an innate but not an adaptive response in celiac disease.

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Structural insights on P31-43, a gliadin peptide able to promote an innate but not an adaptive response in celiac disease.

J Pept Sci. 2019 May;25(5):e3161

Authors: Calvanese L, Nanayakkara M, Aitoro R, Sanseverino M, Tornesello AL, Falcigno L, D'Auria G, Barone MV

Abstract
Inflammation of intestinal tissue in patients affected by celiac disease (CD) originates from the adaptive and innate immune responses elicited by the undigested gliadin fragments through molecular mechanisms not yet completely described. Undigested A-gliadin peptide P31-43 is central to CD pathogenesis, entering enterocytes in vesicular compartments by endocytosis and inducing an innate immune response in CD intestinal mucosa. This study focused on the reasons why P31-43 does not behave as adaptive immunogenic agent. Once obtained by NMR analysis, the three-dimensional model of P31-43 was used to implement a series of in silico experiments aimed to explore the ability of the peptide to interact with HLA-DQ2 and the corresponding receptor onto T cells. Our results show that P31-43 is a poor ligand for DQ2 and/or T-cell receptor. This study was also aimed to investigate, from a structural point of view, the previous experimental findings by which P31-43 is able to enhance the phosphorylation level of the protein ERK2, while some P31-43 Ala-mutants decrease or totally inhibit that process. The molecular models of P31-43, P31-43 P36A, and F37A mutants were used for in silico docking experiments onto the ERK2 structure. The experiments support the hypothesis that P31-43 F37A works as an ERK2 phosphorylation inhibitor because it binds to the ERK2 phosphorylation site. This study reports on the structural properties of so far never NMR characterized gliadin peptides relevant in CD and explores details about their mechanisms of action.

PMID: 30912242 [PubMed - indexed for MEDLINE]

The Reply.

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The Reply.

Am J Med. 2018 05;131(5):e207-e208

Authors: Simons M, Scott-Sheldon LAJ, Ludvigsson JF, Green PHR

PMID: 29673490 [PubMed - indexed for MEDLINE]

Response to Valitutti et al.

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Response to Valitutti et al.

Am J Gastroenterol. 2018 05;113(5):778-779

Authors: Lebwohl B, Ludvigsson JF

PMID: 29681627 [PubMed - indexed for MEDLINE]

Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population.

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Comparison of comorbid diagnoses in children with and without eosinophilic esophagitis in a large population.

Ann Allergy Asthma Immunol. 2018 12;121(6):711-716

Authors: Capucilli P, Cianferoni A, Grundmeier RW, Spergel JM

Abstract
BACKGROUND: Previous reports suggest a higher prevalence of comorbid diseases in patients with eosinophilic esophagitis (EoE), although few have systematically quantified comorbidities in pediatric patients.
OBJECTIVE: To define the rate of comorbid diagnoses in pediatric EoE patients compared with rates in those without EoE.
METHODS: Retrospective cross-sectional review of electronic medical records for patients seen in a single large pediatric primary care network between January 2007 and December 2016 (n = 456,148). International Classification of Diseases, Ninth and Tenth Revision codes were used to determine prevalence rates for coexisting diagnoses.
RESULTS: A total of 428 patients held a diagnosis for EoE. Significant differences in rate of comorbid diseases included allergic rhinoconjunctivitis (60.0% of EoE cohort vs 17.4% of non-EoE cohort, P < .0001); asthma (59.8% of EoE, 21.4% of non-EoE, P < .0001); atopic dermatitis (17.8% of EoE, 6.6% of non-EoE, P < .0001); adrenal insufficiency (2.6% of EoE, 0.4% of non-EoE, P < .0001); autism spectrum disorder (7.5% of EoE, 1.9% of non-EoE, P < .0001); celiac disease (5.6% of EoE, 0.9% of non-EoE, P < .0001); connective tissue diseases (1.4% of EoE, 0.1% of non-EoE, P < .0001); cystic fibrosis (0.9% of EoE, 0.05% of non-EoE, P < .0001); inflammatory bowel disease (0.7% of EoE, 0.2% of non-EoE, P = .03); type 1 diabetes mellitus (1.2% of EoE, 0.3% of non-EoE, P = .0069).
CONCLUSION: Children with EoE have markedly higher rates of both atopic and non-atopic diseases compared with children without EoE. These associations have important implications for comprehensive EoE care and future research regarding associated disease mechanisms.

PMID: 30194971 [PubMed - indexed for MEDLINE]

Phenotypic Expression of Autoimmunity in Children With Autoimmune Thyroid Disorders.

Phenotypic Expression of Autoimmunity in Children With Autoimmune Thyroid Disorders.

Front Endocrinol (Lausanne). 2019;10:476

Authors: Aversa T, Corica D, Zirilli G, Pajno GB, Salzano G, De Luca F, Wasniewska M

Abstract
Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), tend to aggregate with other non-thyroidal autoimmune diseases (NTADs). Aim of this Mini-review is to report the most recent insights concerning the clustering of NTADs in pediatric patients with either HT or GD, the pathophysiology of AITDs and the metamorphic thyroid autoimmunity. A systematic literature research of the last 15 years, according to EQUATOR statement, was carried out through MEDLINE via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) Embase, CINAHL, Cochrane Library, based on the following keywords: (autoimmune thyroid disease OR Hashimoto thyroiditis OR Grave's disease) AND (autoimmune comorbidities OR extra-thyroidal autoimmune disorders) AND (children OR adolescents OR pediatrics) AND (celiac disease OR type 1 diabetes mellitus OR arthropathies OR cutaneous diseases) AND (Turner syndrome OR Down syndrome). One-hundred and twenty-eight manuscripts were extrapolated but only seventeen were eligible. On the basis of the available reports it may be inferred that clustering of NTADs can be significantly modified by both patients' age at AITDs presentation and association with Down's syndrome (DS). Particularly, the association of AITDs with celiac disease and type 1 diabetes was most commonly reported in children than in adults. A sequential shifting from HT to GD has been described in children with AITDs, and it seems to be more frequent in children with DS than in those without DS. Coexistence of autoimmune diseases might be the result of a complex interaction among genetics, environment and epigenetic modifications that are able to affect gene expression, immune system response and, finally, the pathogenesis of autoimmune diseases.

PMID: 31354636 [PubMed]

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