Publications by authors named "Carlo Catassi"

125 Publications

Distribution of celiac disease predisposing genes HLA-DQ2 and HLA-DQ8 in the native population of southern India.

Indian J Gastroenterol 2022 Jun 29. Epub 2022 Jun 29.

Department of Pediatrics, Università Politecnica delle Marche, 60123, Ancona, Italy.

Background: Celiac disease (CD) is an intestinal inflammatory condition caused by the ingestion of gluten peptides in wheat and related grains in individuals carrying HLA-DQ2 and/or HLA-DQ8 genes. In comparison to HLA-DQ8, a higher HLA-DQ2 prevalence is reported in European population where wheat has been the staple food for thousands of years. In non-European population, this pattern of HLA-DQ CD-predisposing gene distribution has not always been found. The aim of this study was to evaluate the HLA-DQ2 and HLA-DQ8 distribution in the native low-gluten consuming southern Indian population.

Methods: Overall, 211 dried blood spots (DBS) were collected from native southern Indian individuals. HLA-DQ characterization and the determination of homozygous/heterozygous status were performed using commercially available HLA-DQ typing kits.

Results: Of 211 collected DBS, 88 (42%, 95% CI: 36-48) were positive for HLA-DQ2 and/or HLA-DQ8 heterodimers. Overall, 40 (19%, 95% CI: 14-24) samples typed positive for HLA-DQ2 and 48 (23%, 95% CI: 18-28) typed positive for HLA-DQ8 genotypes. Of 40 HLA-DQ2-positive individuals, only one subject tested homozygous for the DQB1*02 allele.

Conclusions: In the southern Indian native general population, the prevalence of HLA-DQ8 is higher in comparison to HLA-DQ2 prevalence. This finding could be related to the delayed introduction of wheat in the diet of the southern Indian population.
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http://dx.doi.org/10.1007/s12664-022-01251-6DOI Listing
June 2022

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Nutrients 2022 Jun 15;14(12). Epub 2022 Jun 15.

Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA.

Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. The median VH in NCGS was significantly shorter (600, IQR: 400-705) than controls (900, IQR: 667-1112) ( < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390-620) vs. 427 µm (IQR: 348-569, = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls ( < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. : NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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http://dx.doi.org/10.3390/nu14122487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230100PMC
June 2022

Coeliac disease.

Lancet 2022 06 9;399(10344):2413-2426. Epub 2022 Jun 9.

Department of Specialized Clinical Sciences and Odontostomatology, Polytechnic University of Marche, Ancona, Italy.

Coeliac disease is an autoimmune disorder that primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. Prevalence in the general population ranges from 0·5% to 2%, with an average of about 1%. The development of the coeliac enteropathy depends on a complex immune response to gluten proteins, including both adaptive and innate mechanisms. Clinical presentation of coeliac disease is highly variable and includes classical and non-classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical cases. The disease is associated with a risk of complications, such as osteoporosis and intestinal lymphoma. Diagnosis of coeliac disease requires a positive serology (IgA anti-transglutaminase 2 and anti-endomysial antibodies) and villous atrophy on small-intestinal biopsy. Treatment involves a gluten-free diet; however, owing to the high psychosocial burden of such a diet, research into alternative pharmacological treatments is currently very active.
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http://dx.doi.org/10.1016/S0140-6736(22)00794-2DOI Listing
June 2022

Metabolic Bone Disease in Children with Intestinal Failure and Long-Term Parenteral Nutrition: A Systematic Review.

Nutrients 2022 Feb 26;14(5). Epub 2022 Feb 26.

Department of Pediatrics, Marche Polytechnic University, 60123 Ancona, Italy.

Metabolic bone disease (MBD) is a possible complication of intestinal failure (IF), with a multi-factorial pathogenesis. The reduction of bone density (BMD) may be radiologically evident before manifestation of clinical signs (bone pain, vertebral compression, and fractures). Diagnosis relies on dual-energy X-ray absorptiometry (DXA). Incidence and evolution of MBD are not homogeneously reported in children. The aim of this systematic review was to define the prevalence of MBD in IF children and to describe risk factors for its development. A comprehensive search of electronic bibliographic databases up to December 2021 was conducted. Randomized controlled trials; observational, cross-sectional, and retrospective studies; and case series published between 1970 and 2021 were included. Twenty observational studies (six case-control) were identified and mostly reported definitions of MBD based on DXA parameters. Although the prevalence and definition of MBD was largely heterogeneous, low BMD was found in up to 45% of IF children and correlated with age, growth failure, and specific IF etiologies. Data demonstrate that long-term follow-up with repeated DXA and calcium balance assessment is warranted in IF children even when PN dependence is resolved. Etiology and outcomes of MBD will be better defined by longitudinal prospective studies focused on prognosis and therapeutic perspectives.
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http://dx.doi.org/10.3390/nu14050995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912854PMC
February 2022

A new phenotype of aldolase a deficiency in a 14 year-old boy with epilepsy and rhabdomyolysis - case report.

Ital J Pediatr 2022 Mar 4;48(1):39. Epub 2022 Mar 4.

Division of Metabolism, Department of Pediatric Subspecialties, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

Background: Glycogen storage disease type XII is a rare metabolic disease resulting from Aldolase A deficiency that causes muscle glycogen accumulation, with crisis of rhabdomyolysis and hemolytic anemia. In the very few cases described, rhabdomyolysis crises are caused by fever and/or exercise and can accompany acute hemolytic anemia. Although currently there is no therapy available for this disease, the guidelines for the management of other forms of glycogen storage diseases recommend a nutritional therapy in order to avoid hypoglycemia or prevent exercise-induced rhabdomyolysis.

Case Presentation: In this case report we describe a new phenotype of the disease in a 14-year-old boy, characterized by seizures and rhabdomyolysis. Beside an antiepileptic treatment, we propose a new therapeutic approach based on ketogenic diet in order to supply an energetic substrate for skeletal muscle and neurons.

Conclusions: The anti-epileptic therapy and the dietetic approach were well tolerated by the patient who showed good compliance. This led to a deceleration of the disease with no other acute episodes of seizures and rhabdomyolysis, without any side effects observed.
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http://dx.doi.org/10.1186/s13052-022-01228-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895104PMC
March 2022

Circulating microRNAs as novel non-invasive biomarkers of paediatric celiac disease and adherence to gluten-free diet.

EBioMedicine 2022 Feb 9;76:103851. Epub 2022 Feb 9.

Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy. Electronic address:

Background: Celiac Disease (CD) is a multifactorial autoimmune enteropathy (with a prevalence of approximately 1% worldwide) that exhibits a wide spectrum of clinical, serological and histological manifestations. For the diagnosis of paediatric CD, the gold standard is the combination of serological tests (with high TGA-IgA values greater than 10 times the upper limit of normal) and duodenal biopsy (with a positive TGA-IgA but low titer). Therefore, a diagnostic test that totally excludes an invasive approach has not been discovered so far and the discovery of novel biological markers would represent an undoubted advantage for the diagnosis of CD and prognostic evaluation. MicroRNAs (miRNAs), small non-coding RNAs (18-22 nucleotides) that regulate gene expression at post-transcriptional level and play important roles in many biological processes, represent a novel class of potential disease biomarkers. Their presence in biological fluids (i.e., serum, plasma, saliva, urine) provides the opportunity to employ circulating miRNAs as novel non-invasive biomarkers.

Methods: In our prospective observational study, we examined the expression of circulating miRNAs in a cohort of CD patients (both at diagnosis and on gluten-free diet, respectively referred as CD and GFD) compared to healthy controls. By small RNA-Seq we discovered a set of circulating miRNAs that were further validated by qPCR with specific assays.

Findings: We found that out of the 13 miRNAs able to discriminate the three groups (i.e., CD, GFD and controls), three of them, namely miR-192-5p, miR-215-5p and miR-125b-5p (alone or in combination), were able to discriminate these three groups with high accuracy and specificity.

Interpretation: Our conclusions emphasize that these circulating miRNAs can be employed not only for the diagnosis of CD patients with a low TGA-IgA titer but also to monitor the adherence to a gluten-free diet by CD patients. In conclusion, we suggest the use of the circulating miRNAs identified in this work as a novel diagnostic and follow-up tool for paediatric CD.

Funding: This work was supported by Fondazione Celiachia Onlus (FC) Grant n° 018/FC/2013 and by Italian Ministry of Health (Ricerca Corrente).
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http://dx.doi.org/10.1016/j.ebiom.2022.103851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842006PMC
February 2022

Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

Nutrients 2021 Dec 21;14(1). Epub 2021 Dec 21.

Department of Pediatrics, Marche Polytechnic University, 60123 Ancona, Italy.

The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.
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http://dx.doi.org/10.3390/nu14010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746847PMC
December 2021

The global burden of coeliac disease: opportunities and challenges.

Nat Rev Gastroenterol Hepatol 2022 05 3;19(5):313-327. Epub 2022 Jan 3.

Universidad del Salvador, Buenos Aires, Argentina.

Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.
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http://dx.doi.org/10.1038/s41575-021-00552-zDOI Listing
May 2022

The Clinical Spectrum of Inflammatory Bowel Disease Associated With Specific Genetic Syndromes: Two Novel Pediatric Cases and a Systematic Review.

Front Pediatr 2021 26;9:742830. Epub 2021 Oct 26.

Department of Pediatrics, Polytechnic University of Marche, G. Salesi Children's Hospital, Ancona, Italy.

Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific genetic syndromes associated with a risk of autoimmune disorders. We aimed to systematically evaluate the prevalence of IBD in specific genetic syndromes and to review the clinical characteristics of the published cases. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies describing patients with IBD and a genetic syndrome and/or studies indicating the prevalence or incidence of IBD in subjects with a genetic syndrome were included. Forty-six studies describing a total of 67 cases of IBD in six genetic syndromes and two personally assessed unpublished cases were included in the review. The majority of cases were associated with Turner syndrome (TS) (38 cases), Down syndrome (DS) (18 cases) and neurofibromatosis type 1 (NF1) (8 cases). Sporadic cases were described in DiGeorge syndrome (2), Kabuki syndrome (2), and Williams syndrome (1). The prevalence of IBD ranged from 0.67 to 4% in TS and from 0.2 to 1.57% in DS. The incidence of IBD was increased in TS and DS compared to the general population. Eight cases of IBD in TS had a severe/lethal course, many of which described before the year 2000. Two IBD cases in DS were particularly severe. Evidence of a greater prevalence of IBD is accumulating in TS, DS, and NF1. Management of IBD in patients with these genetic conditions should consider the presence of comorbidities and possible drug toxicities. : PROSPERO, identifier: CRD42021249820.
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http://dx.doi.org/10.3389/fped.2021.742830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576358PMC
October 2021

The surprising 'Coeliac Chinese box' from Italy.

Gastroenterol Rep (Oxf) 2021 Oct 30;9(5):478-479. Epub 2021 Jan 30.

Department of Pediatrics, Marche Polytechnic University, Ancona, Italy.

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http://dx.doi.org/10.1093/gastro/goaa093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560033PMC
October 2021

Current Status and Perspectives on the Application of CRISPR/Cas9 Gene-Editing System to Develop a Low-Gluten, Non-Transgenic Wheat Variety.

Foods 2021 Oct 2;10(10). Epub 2021 Oct 2.

Division of Pediatrics, DISCO Department, Polytechnic University of Marche, 60123 Ancona, Italy.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods have not been sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, has succeeded in the development of safer wheat varieties. However, these varieties have multiple challenges in terms of their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed the published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in terms of editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of a celiac-safe wheat variety and to establish it as a "tool to celiac safe wheat".
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http://dx.doi.org/10.3390/foods10102351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534962PMC
October 2021

Determination of Urinary Gluten Immunogenic Peptides to Assess Adherence to the Gluten-Free Diet: A Randomized, Double-Blind, Controlled Study.

Clin Transl Gastroenterol 2021 10 6;12(10):e00411. Epub 2021 Oct 6.

Division of Pediatrics, DISCO Department, Polytechnic University of Marche, Ancona, Italy.

Introduction: The adherence to a gluten-free diet (GFD) is a trending topic in the management of celiac disease. The aim of our study was to evaluate the diagnostic performance of urinary gluten immunogenic peptides (GIP) determination to detect gluten contamination of the GFD.

Methods: In study A, 25 healthy adults on a standard GFD performed 6 gluten challenges (0, 10, 50, 100, 500, and 1,000 mg) with quantification of urinary GIP before (T0) and during the following 24 hours. In study B, 12 participants on a gluten contamination elimination diet underwent urinary GIP determination at T0 and after challenge with 5 or 10 mg gluten. Urine GIP concentration was determined by an immunochromatographic assay.

Results: In study A, 51 of 150 baseline urine samples were GIP+ on GFD and 7 of 17 were GIP+ after the zero-gluten challenge, whereas only 55 of 81 were GIP+ after the 10-1,000 mg gluten challenges. There was no significant change in the 24-hour urinary GIP when increasing gluten from 10 to 1,000 mg. In study B, 24 of 24 baseline urine samples were GIP-, whereas 8 of 24 were GIP+ after 5 or 10 mg of gluten.

Discussion: Traces of gluten in the standard GFD may cause positivity of urinary GIP determination, whereas a false negativity is common after a gluten intake of 10-1,000 mg. Owing to the impossibility of standardizing the test in normal conditions, it seems unlikely that urinary GIP determination may represent a reliable tool to assess the compliance to the GFD of patients with celiac disease or other gluten-related disorders.
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http://dx.doi.org/10.14309/ctg.0000000000000411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500619PMC
October 2021

Factors associated with quality of life in Italian children and adolescents with IBD.

Sci Rep 2021 09 10;11(1):18076. Epub 2021 Sep 10.

Department of Pediatrics, Polytechnic University of Marche, G. Salesi Children's Hospital, Via Corridoni 11, 60123, Ancona, Italy.

Improving the quality of life (QoL) is crucial in the management of pediatric inflammatory bowel disease (IBD). We aimed to (1) Validate the IMPACT-III questionnaire in Italian IBD children; (2) explore factors associated to QoL in pediatric IBD. Internal consistency, concurrent validity, discriminant validity and reproducibility of the Italian version of the IMPACT-III questionnaire was measured in IBD children/adolescents in 8 centers. Associations between patient and disease characteristics and the IMPACT-III domains were analyzed through quantile regression analysis. The IMPACT-III questionnaire, collected in 282 children with IBD (median age: 14.8 years; IQR 12.4-16.4) showed a median total score of 76 (IQR 67-83). Female gender, active disease and age were negatively associated with the total IMPACT-III score. Specifically, female gender was negatively associated with the Bowel/Systemic Symptoms, Emotional and Treatment domain scores, while disease activity was significantly associated with Bowel Symptoms and Treatment/Interventions reported QoL. The IMPACT- III showed good internal consistency (Cronbach's alpha coefficient = 0.87, 95% CI 0.85-0.89) and reproducibility (Concordance Correlation Coefficient = 0.66, 95% CI 0.57-0.74). In Italian children with IBD active disease, female gender and adolescence are associated to a worse QoL, indicating the need of more attention in this subgroup of young patients. IMPACT-III questionnaire is a reliable instrument to measure QoL in Italian children.
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http://dx.doi.org/10.1038/s41598-021-97661-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433211PMC
September 2021

Wheat consumption and prevalence of celiac disease: Correlation from a multilevel analysis.

Crit Rev Food Sci Nutr 2021 Jun 29:1-15. Epub 2021 Jun 29.

Department of Pediatrics, Polytechnic University of Marche, Ancona, Italy.

Celiac disease (CD) is triggered by both genetic and environmental factors. More than 1% of the world's population is affected by CD. In recent years, studies have confirmed a worldwide rising trend in CD prevalence. "Westernized diet" is one of the main factors of this increasing prevalence. However, the relationship between wheat consumption, its dynamics, and CD has not been adequately investigated on a global scale. This study aimed to perform a multilevel analysis of the association between wheat consumption and CD. Wheat consumption data from countries and continents were obtained from the database. The relative increase/decrease in wheat consumption over a long period (since 1961) and a short period (since 2004) were calculated using various statistical tools. The relationship between wheat consumption and celiac frequency was determined using the R-commander R package version 2.6-2. Pearson's correlation coefficient (r = 0.88) confirmed a high positive correlation between wheat consumption and the prevalence of biopsy-proven CD by estimating continent-wide wheat consumption data, but an insignificant correlation was found when the data were compared country-wide.
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http://dx.doi.org/10.1080/10408398.2021.1939650DOI Listing
June 2021

Navigating celiac disease and the gluten-free diet in China.

Nutr Health 2021 Dec 11;27(4):395-403. Epub 2021 Apr 11.

Celiac Disease Center, 21611Columbia University Irving Medical Center, USA.

Background: Little is known about celiac disease (CeD) diagnosis and management in China.

Aim: This pilot aimed to be the first study to describe, quantitatively and qualitatively, how individuals living in China navigate CeD and the gluten-free diet (GFD).

Methods: Participants were 13 adults and four parents of children with reported CeD, recruited from 11 mainland China cities via an online GFD support group. CeD-specific quality of life (CD-QOL and CD-PQOL) and diet adherence (CDAT) were assessed. In-depth interviews addressed experiences with CeD and the GFD.

Results: Six of 17 participants reported biopsy- or serology-confirmed CeD. The mean (SD) adult CDAT score was 15.2 (3.6), > 13 indicating inadequate GFD adherence. The mean adult CD-QOL score was 62.1 (24.1) out of 100, in the "medium" to "good" range. Results were similar in children. Major interview themes included: (1) a challenging journey to obtain diagnosis; (2) social and structural barriers to maintaining the GFD; and (3) reliance on self in management of CeD.

Conclusion: Obtaining a diagnosis, maintaining a GFD, and living with CeD can be extremely challenging in mainland China. Results suggest an urgent need for CeD-specific education and Asian-adapted GFD guidance for both healthcare practitioners and patients.
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http://dx.doi.org/10.1177/0260106021990254DOI Listing
December 2021

Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease.

Nutrients 2021 Jan 9;13(1). Epub 2021 Jan 9.

Division of Pediatrics, DISCO Department, Polytechnic University of Marche, 60123 Ancona, Italy.

A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2-18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5-20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.
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http://dx.doi.org/10.3390/nu13010190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827942PMC
January 2021

Prevalence of COVID-19 in Italian Children With Celiac Disease: A Cross-Sectional Study.

Clin Gastroenterol Hepatol 2021 05 3;19(5):1075. Epub 2020 Dec 3.

Center for Celiac Research and Treatment, Massachusetts General Hospital for Children, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.cgh.2020.11.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713539PMC
May 2021

Adherence to the Gluten-Free Diet during the Lockdown for COVID-19 Pandemic: A Web-Based Survey of Italian Subjects with Celiac Disease.

Nutrients 2020 Nov 12;12(11). Epub 2020 Nov 12.

Department of Pediatrics, Marche Polytechnic University, 60020 Ancona, Italy.

We aimed to assess the perceived impact of the lockdown, imposed to control the spreading of COVID-19, on the adherence of Italian celiac disease (CD) subjects to the gluten-free diet by a web-based survey. A total of 1983 responses were analyzed, 1614 (81.4%) by CD adults and 369 (18.6%) by parents/caregivers of CD children/adolescents. The compliance with the GFD was unchanged for 69% of the adults and 70% of the children, and improved for 29% of both. The factors increasing the probability to report stricter compliance were the presence of CD symptoms in the last year before the lockdown (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.46-2.26), a partial usual adherence to gluten-free diet (GFD) (OR 1.91, 95% CI 1.2-3.06), and having tried recipes with naturally gluten-free ingredients more than usual (OR 1.58, 95% CI 1.28-1.96) for adults; the presence of CD symptoms in the last year (OR 2.05, 95% CI 1.21-3.47), still positive CD antibodies (OR 1.89, 95% CI 1.14-3.13), and other family members with CD (OR 2.24, 95% CI 1.3-3.85) for children/adolescents. Therefore, the lockdown led to a reported improved adherence to the GFD in one-third of the respondents, in particular in those with previous worse disease control, offering the opportunity to avoid sources of contamination/transgression and increase the use of naturally gluten-free products.
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http://dx.doi.org/10.3390/nu12113467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698218PMC
November 2020

Early biochemical effects of velmanase alfa in a 7-month-old infant with alpha-mannosidosis.

JIMD Rep 2020 Sep 10;55(1):15-21. Epub 2020 Jul 10.

Department of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona Italy.

Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasible therapeutic option. Only in 2018, the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long-term treatment of non-neurological manifestations in mild and moderate forms of alpha-mannosidosis. In this study, the very early biochemical effects of enzyme replacement therapy in in a 7-month-old patient with alpha-mannosidosis were described. Velmanase alpha was administered as supporting therapy awaiting for hematopoietic stem cell transplantation, the treatment chosen for the patient because of the early onset form. The results showed that the enzyme replacement therapy was able to reduce the content of three different mannosyl-oligosaccharides monitored by tandem mass spectrometry after 2 months of treatment. In particular, the mean relative changes from baseline values were -67% in urine and -53% in serum at the latest observation. The study also showed that the enzymatic activity detected in serum 1 week after the first infusion was four times higher than the normal values and constant in the following points of observation. These findings led us to assume that velmanase alfa might be biologically active in this young patient.
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http://dx.doi.org/10.1002/jmd2.12144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463052PMC
September 2020

Lower Level of Plasma 25-Hydroxyvitamin D in Children at Diagnosis of Celiac Disease Compared with Healthy Subjects: A Case-Control Study.

J Pediatr 2021 01 2;228:132-137.e1. Epub 2020 Sep 2.

Department of Pediatrics, Marche Polytechnic University, Ancona, Italy; Center for Celiac Research, Mass General Hospital for Children, Boston, MA.

Objective: To evaluate the vitamin D status of children with a new diagnosis of celiac disease compared with healthy controls.

Study Design: This was a case-control study. Cases were consecutive children with newly diagnosed celiac disease. Controls were healthy children matched for age, sex, ethnicity, and month of blood testing. Plasma 25-hydroxyvitamin D (25-OHD) was measured as the index of vitamin D nutritional status. The Student t test was used for comparisons. Differences in frequencies were evaluated with the χ test. Associations between variables were estimated by calculating Pearson correlation coefficients.

Results: There were 131 children with celiac disease enrolled (62% females; mean age 8.1 ± 1.1 years). The control group included 131 healthy children (62% females; mean age 8.2 ± 1.2). All were of European origin. Plasma 25-OHD levels were significantly lower in patients than in controls (25.3 ± 8.0 and 31.6 ± 13.7 ng/mL; P < .0001). The percentage of children with vitamin D deficiency (<20 ng/mL) was significantly higher in children with celiac diseaseas compared with controls (31% vs 12%; P < .0001). The concentration of 25-OHD was significantly lower in patients than in controls during summer (P < .01) and autumn (P < .0001).

Conclusions: In this case-control study, at diagnosis, children with celiac disease showed lower levels of plasma 25-OHD compared with healthy subjects. Vitamin D status should be checked at diagnosis of celiac disease, particularly during summer and fall months.
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http://dx.doi.org/10.1016/j.jpeds.2020.08.089DOI Listing
January 2021

A negative fallout of COVID-19 lockdown in Italy: Life-threatening delay in the diagnosis of celiac disease.

Dig Liver Dis 2020 10 16;52(10):1092-1093. Epub 2020 May 16.

Department of Pediatrics, Polytechnic University of Marche, Ancona, Italy; Center for Celiac Research and Treatment, Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229920PMC
October 2020

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity.

Front Nutr 2020 17;7:29. Epub 2020 Mar 17.

biotask AG, Esslingen, Germany.

Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis.
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http://dx.doi.org/10.3389/fnut.2020.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090026PMC
March 2020

Nutritional Status, Dietary Intake, and Adherence to the Mediterranean Diet of Children with Celiac Disease on a Gluten-Free Diet: A Case-Control Prospective Study.

Nutrients 2020 Jan 4;12(1). Epub 2020 Jan 4.

Department of Pediatrics, Marche Polytechnic University, 60123 Ancona, Italy.

The only effective treatment for celiac disease (CD) is a life-long strict gluten-free diet (GFD). Nutritional adequacy of the GFD has remained controversial and a matter of debate for a long time. No large case-control studies on children regarding the nutritional adequacy of the GFD has been performed. In this study, children diagnosed with CD on a GFD for ≥ 2 years were recruited. Controls were age and gender-matched healthy children not affected with CD. In both groups, anthropometric measurements and energy expenditure information were collected. Dietary assessment was performed by a 3-day food diary. Adherence to the Mediterranean diet was estimated by the KIDMED index. Overall, 120 children with CD and 100 healthy children were enrolled. No differences were found between CD children and controls in anthropometric measurements and energy expenditure. In the CD group, the daily intake of fats was significantly higher while the consumption of fiber was lower in comparison with the control group. The median KIDMED index was 6.5 in CD children and 6.8 in healthy controls. The diet of children with CD in this study was nutritionally less balanced than controls, with a higher intake of fat and a lower intake of fiber, highlighting the need for dietary counseling.
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http://dx.doi.org/10.3390/nu12010143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019969PMC
January 2020

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

Dig Liver Dis 2019 11 3;51(11):1547-1550. Epub 2019 Aug 3.

Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Center for Celiac Research and Treatment, Mass General Hospital for Children, Boston, MA 02114, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.dld.2019.06.016DOI Listing
November 2019

Celiac disease: a comprehensive current review.

BMC Med 2019 07 23;17(1):142. Epub 2019 Jul 23.

Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA, 02114, USA.

Background: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options.

Main Body: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma.

Conclusions: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
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http://dx.doi.org/10.1186/s12916-019-1380-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647104PMC
July 2019

Increased Prevalence of Celiac Disease in School-age Children in Italy.

Clin Gastroenterol Hepatol 2020 03 17;18(3):596-603. Epub 2019 Jun 17.

Department of Pediatrics, Marche Polytechnic University, Ancona, Italy; Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background & Aims: Celiac disease is one of the most common diseases worldwide, with an apparent trend of increasing prevalence. We investigated the prevalence of celiac disease in children in Italy in 2015-2016 and compared that with data from 25 years ago.

Methods: We screened 4570 children (5-11 years old, 80.1% of the eligible population) from metropolitan areas of Ancona and Verona for HLA genes associated with increased risk of celiac disease, and for total serum levels of IgA and IgA class anti-tissue transglutaminase in HLA positives. Diagnoses of celiac disease were confirmed by detection of anti-endomysial antibody and analysis of intestinal biopsies. The prevalence of celiac autoimmunity and celiac disease were calculated and compared with values from the same geographical area during the years 1993-1995, after adjustment for the different diagnostic algorithm.

Results: We identified 1960 children with celiac disease-associated haplotypes (43% of children screened; 95% CI, 40.8%-45.2%). The prevalence of celiac disease autoimmunity in the HLA-positive subjects was 96/1706 (5.62%; 95% CI, 4.53%-6.71%) and 54 of these children satisfied the diagnostic criteria for celiac disease. In the eligible population there were other 23 known cases of celiac disease. The overall estimated prevalence of celiac disease was 1.58% (95% CI, 1.26%-1.90%); this value is significantly higher than the 1993-1995 adjusted prevalence (0.88%; 95% CI, 0.74%-1.02%).

Conclusions: We found the prevalence of celiac disease in children in Italy to be greater than 1.5%; this value has increased significantly over the past 25 years. Studies are needed to determine the causes of this large increase.
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http://dx.doi.org/10.1016/j.cgh.2019.06.013DOI Listing
March 2020

Celiac Disease Prevalence is Increased in Primary Sjögren's Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study.

J Clin Med 2019 Apr 19;8(4). Epub 2019 Apr 19.

Rheumatology Unit, Department of Medicine, University of Perugia, 06128 Perugia, Italy .

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, = 0.058) and SSc (1.34%, = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc-CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.
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http://dx.doi.org/10.3390/jcm8040540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517955PMC
April 2019
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