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Significance The incidence of chronic inflammatory autoimmune conditions, such as celiac disease (CD), is increasing at an alarming rate. CD is the only autoimmune condition for which the trigger, gluten, is known. However, its etiology and pathogenesis remain incompletely defined as recent studies suggest other environmental stimuli may play a key role in CD pathogenesis. Here, we prospectively examine the trajectory of the gut microbiota starting 18 mo before CD onset in 10 infants who developed CD and 10 infants who did not. We identified alterations in the gut microbiota, functional pathways, and metabolome before CD onset, suggesting our approach may be used for disease prediction with the ultimate goal of identifying early preventive interventions to reestablish tolerance and prevent autoimmunity., Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.

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

The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at-risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at-risk infants long time before any symptom or production of antibodies.We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at-risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4-19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten-free diet. At similar age points, controls were also evaluated.Three genes (KIAA, TAGAP [T-cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G-protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of patients.The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.

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.

BACKGROUND Iodine is an essential micronutrient for intellectual development in children. Information on iodine intakes based on 24-h urinary iodine excretion (UIE) is scant, because iodine status is only assessed by the measurement of urinary iodine concentration (UIC) in spot urine samples. OBJECTIVES The aim of our study was to evaluate the iodine intake of school-age children and adolescents, using UIE measurement in 24-h urine collections. METHODS The study population included 1270 healthy subjects (677 boys, 593 girls) aged 6-18 y (mean age ± SD: 10.3 ± 2.9) from 10 Italian regions. Daily iodine intake was estimated as UIE/0.92, based on the notion that $\sim$92% of the dietary iodine intake is absorbed. The adequacy of intakes was assessed according to the Dietary Reference Values for iodine of the European Food Safety Authority (EFSA). Body mass index (BMI) and UIC were also measured for each subject. RESULTS Based on the scientific opinion of EFSA, 600 of 1270 subjects (47.2%) had a lower than adequate iodine intake, with a higher prevalence among girls (54.6%) compared with boys (40.2%) (P

Background Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in genes involved in low-density lipoprotein (LDL) uptake (LDLR, APOB and PCSK9). Genetic diagnosis is particularly useful in asymptomatic children allowing for the detection of definite FH patients. Furthermore, defining their genetic status may be of considerable importance as the compound heterozygous status is much more severe than the heterozygous one. Our study aims at depicting the genetic background of an Italian pediatric population with FH focusing on the correlation between lipid profile and genetic status. Methods Out of 196 patients with clinically suspected FH (LDL-cholesterol [LDL-C] levels above 3.37 mmol/L, cholesterol level above 6.46 mmol/L in a first-degree relative or the presence of premature cardiovascular acute disease in a first/second-degree relative), we screened 164 index cases for mutations in the LDLR, APOB and PCSK9 genes. Results Patients with mutations (129/164) showed increased levels of LDL-C, 95th percentile-adjusted LDL-C and LDL/high-density lipoprotein (HDL) ratio and decreased levels of HDL-C, adjusted HDL-C. The association of the LDL/HDL ratio with the presence of mutations was assessed independently of age, (body mass index) BMI, parental hypercholesterolemia, premature coronary artery disease (CAD), triglycerides by multivariate logistic regression (odds ratio [OR]=1.701 [1.103–2.621], p=0.016). The LDL/HDL ratio gradually increased from patients without mutations to patients with missense mutations, null mutations and compound heterozygotes. Conclusions In conclusion, the LDL/HDL ratio proved to be a better parameter than LDL-C for discriminating patients with from patients without mutations across different genetic statuses.

As of now, no established model for the transition from childhood to adulthood in coeliac disease exists. We aim to describe the dietary compliance and the quality of life of a population of young coeliac disease patients around transition age and to develop a practical tool (TRANSIT-CeD disk) which can be used during the transition process effectively to transmit young adults to the adult healthcare giver.We consecutively recruited all coeliac disease patients with a paediatric diagnosis (≤16 years) and aged between 9 and 20 years at the time of the study. The patients were asked to answer some questions concerning their adherence to a gluten-free diet, knowledge about coeliac disease, relationship with healthcare givers and quality of life.We included 58 subjects, mean age 14.5 ± 3.6 years, of which 62% were girls/young women. We observed that dietary compliance was independently and positively related to age at diagnosis and coeliac disease knowledge, while quality of life was only independently and positively related to coeliac disease knowledge.A good coeliac disease knowledge is positively related to dietary compliance and quality of life. With the help of the TRANSIT-CeD disk we proposed, paediatricians and adult gastroenterologists can follow the patients during the transition and identify some points to work on.

BACKGROUND AND OBJECTIVES: The increasing incidence of celiac disease (CD) suggests that common infections before the onset of autoimmune diseases could be an important factor in switching the immune response. We aimed to explore the relationship between early clinical events and the development of CD in genetically predisposed infants. METHODS: In this study, 373 newborns from families with at least 1 relative with CD were recruited, and human leukocyte antigen DQ2- or DQ8-positive infants were followed up with clinical and serological evaluations. Cross tabulation and odds ratios were used to explore the risk associated with single variables, and logistic regression analysis was performed to determine the variables that contributed to the risk of developing CD. Stepwise discriminant analysis was used to determine which variables could distinguish case patients from controls before diagnosis. RESULTS: The cumulative incidence of CD in this cohort was 6% at 3 years and 13.5% at 5 years of age, and l34 children (14%) developed CD before the sixth year of life. An analysis of adverse events showed a higher frequency of respiratory tract infections among CD patients during the first 24 months of life. In a stepwise discriminant analysis, which included sex and human leukocyte antigen risk class, only respiratory infections in the second and first years of life significantly contributed to discrimination of case patients versus controls. CONCLUSIONS: A multivariate model of discriminant analysis showed that the frequency of respiratory infections in the first 2 years of life could distinguish children who developed CD from those who did not.

Background Newborns at high risk of celiac disease (CD) were recruited in Italy in the context of the PreventCD study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T-cell reactivity to gliadin at the first clinical and/or serological signs of CD. Methods Gliadin-reactive T-cell lines were generated from intestinal biopsies of 19 HLA-DQ2-or HLA-DQ8-positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls. Immune reactivity was evaluated against gliadin and known immunogenic peptides from α-, γ-, or ω-gliadins. The role of deamidation by transglutaminase (tTG) in determining the immunogenicity of gliadin was also investigated. Results Most of the children with CD (either acute or potential) had an inflammatory response to gliadin. Notably, signs of T-cell reactivity to gliadin were also found in some non-celiac subjects, in which IFN-γ responses occurred mainly when regulatory IL-10 and TGF-β cytokines were blocked. Interestingly, PreventCD children reacted to gliadin peptides found active in adult CD patients, and tTG deamidation markedly enhanced gliadin recognition. Conclusions T cells reactive to gliadin can be detected in the intestine of children at high risk of developing CD, in some cases also in the presence of a normal mucosa and negative CD-associated antibodies. Furthermore, children at a very early stage of CD recognize the same gliadin epitopes that are active in adult CD patients. Tissue transglutaminase strongly enhances gluten T-cell immunogenicity in early CD.

A gluten-free diet (GFD) is currently the only available treatment for patients with celiac disease (CD). Several clinical trials have demonstrated that most celiac patients can tolerate a medium-high quantity of oats without any negative clinical effects, however, the inclusion of oats in GFD is still a matter of debate. In this study, Italian children with CD were enrolled in a 15-month, randomized, double-blind, placebo-controlled multicenter trial. Participants were randomized in two groups following either A-B treatment (6 months of diet “A”, 3 months of standard GFD, 6 months of diet “B”), or B-A treatment (6 months of diet “B”, 3 months of standard GFD, 6 months of diet “A”). A and B diets included gluten-free (GF) products (flour, pasta, biscuits, cakes and crisp toasts) with either purified oats or placebo. Clinical data (Gastrointestinal Symptoms Rate Scale [GSRS] score) and intestinal permeability tests (IPT), were measured through the study period. Although the study is still blinded, no significant differences were found in GSRS score or the urinary lactulose/mannitol (L/M) ratio between the two groups after 6 months of treatment. These preliminary results suggest that the addition of non-contaminated oats from selected varieties in the treatment of children with CD does not determine changes in intestinal permeability and gastrointestinal symptoms.

A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse ( 𝑃 = 0 . 0 4 ) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, 𝑃 = 0 . 0 6 ). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA ( 𝑃 = 0 . 6 3 ), Marsh-Oberhuber grading ( 𝑃 = 0 . 0 8 ), or intestinal IFN-γ mRNA ( 𝑃 > 0 . 0 5 ). Creatinine clearance did not vary after 90 days of treatment ( 𝑃 = 0 . 4 6 ). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.

See editorial on page 284. BACKGROUND & AIMS: The presence of celiac diseaseassociated autoantibodies (antiendomysium and antitissue transglutaminase [anti-TG2]) with normal jejunal mucosa indicate potential celiac disease. We performed a prospective, 3-year cohort study to determine the natural history of potential celiac disease in children. METHODS: The study included 106 children with potential celiac disease, based on serology analysis and normal duodenal architecture. All but 2 carried the HLA-DQ2 and/or DQ8 haplotype. In all children, every 6 months, growth, nutritional parameters, celiac disease serology, and autoimmunity were investigated. In biopsies, intraepithelial-, CD3-, and lamina propria CD25-positive cells were counted; duodenal deposits of anti-TG2 immunoglobulin A were detected. Biopsy analysis was repeated after 2 years on patients with persistent positive serology and/or symptoms. RESULTS: Celiac disease was detected primarily in firstdegree relatives and patients with autoimmune disorders (40.6%). A gluten-free diet was prescribed to 20/106 patients because of symptoms, which were relieved in only 11. Eightynine of the 106 patients entered the follow-up study, with normal daily consumption of gluten. During the follow-up antibodies disappeared in 14.6% and fluctuated in 32.6%. Villous atrophy was observed in 12/39 patients (30.8%) who underwent a repeat biopsy. CONCLUSIONS: Most children with potential celiac disease remain healthy. After 3 years, approximately 33% of patients develop villous atrophy. Intestinal deposits of anti-TG2 IgA identify children at risk for villous atrophy.

Objective To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease. Study design This noninferiority clinical trial used a double-blind, placebo-controlled, crossover design extended over 15 months. Three hundred six children with a biopsy-proven diagnosis of celiac disease on a gluten-free diet for ≥2 years were randomly assigned to eat specifically prepared gluten-free food containing an age-dependent amount (15-40 g) of either placebo or purified nonreactive varieties of oats for 2 consecutive 6-month periods separated by washout standard gluten-free diet for 3 months. Clinical (body mass index, Gastrointestinal Symptoms Rating Scale score), serologic (IgA antitransglutaminase antibodies, and IgA anti-avenin antibodies), and intestinal permeability data were measured at baseline, and after 6, 9, and 15 months. Direct treatment effect was evaluated by a nonparametric approach using medians (95% CI) as summary statistic. Results After the exclusion of 129 patients who dropped out, the cohort included 177 children (79 in the oats–placebo and 98 in the placebo–oats group; median, 0.004; 95% CI, −0.0002 to 0.0089). Direct treatment effect was not statistically significant for clinical, serologic, and intestinal permeability variables (body mass index: median, −0.5; 95% CI, −0.12 to 0.00; Gastrointestinal Symptoms Rating Scale score: median, 0; 95% CI, −2.5 to 0.00; IgA antitransglutaminase antibodies: median, −0.02; 95% CI, −0.25 to 0.23; IgA anti-avenin antibodies: median, −0.0002; 95% CI, −0.0007 to 0.0003; intestinal permeability test: median, 0.004; 95% CI, −0.0002 to 0.0089). Conclusions Pure nonreactive oat products are a safe dietary choice in the treatment of children with celiac disease. Trial registration ClinicalTrials.gov : NCT00808301 .

Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.

OBJECTIVE. Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor–induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker–treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. METHODS. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4–36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. RESULTS. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. CONCLUSIONS. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

s / Digestive and Liver Disease 46 (2014) e85–e127 e95 4.5±0.6pg/ml, mean FT4 1.2± .4 ng/dl. TSH levels were above cutoff laboratory range in 10% of our population and the 2 patients (0.2%) of the whole population presented TSH≥10 UI/ml. We found a significant positive correlation between TSH levels and BMI z-score (rho=0.121, p=0.001), even after adjustment for age and sex (r=0.117, p=0.001); a positive correlation was also observed between FT3 and BMI z-score (rho=0.161, p

s / Digestive and Liver Disease 45 (2013) e263–e311 e295 Conclusions: The association of s-ATI with trough s-IFX levels and response to therapy has been inconsistent due to a difficulty of standardization of methods of measurement of serum IFX or antidrug antibodies. There are lack data in pediatric population. Combined measurements of IFX and ATI using our cut-off levels has provided high accuracy for discriminating between responder and not-responder patients. The presence of detectable drug in the serum typically impairs the performance of a solid-phase enzymelinked immunosorbent assay (ELISA) andwestern blot.With classic ELISA, antibodies remainundetectable as long as thedrug is present in the blood. The type of detection assays also affects the reported incidence of ATIs. Our method is rapid, accurate and reproducible even if it is necessary to validate it on a larger population. Immunogenicityof IFX is apotentialmajor limitationof this class of drugand for clinicians, the loss of clinical remission due to immunogenicity is a important target especially in pediatric population.

and 6 months (6mo). PCDAI was calculated at the beginning and at 6 months. Statistical analysis was performed using Student’s t test and the value of p< 0.05 was considered statistically significant. Calprotectin mean value was 1296.4±1203.8mcg/ml at the onset, 645.9±623.8 at 1 month (p< 0.05); 633.6±722.5 (p< 0.05) at 3 months; 642.89±532.00 (p< 0.05) at 6 months. PCDAI of all patients was 20.00±4.5 at the beginning of NT, 14.8±5.5 at 6mo (p< 0.05), that indicates reduction of values, but not complete clinical remission (PCDAI

child, whose parents were consanguineous. He was admitted to our hospital for bloody diarrhoea, asthenia, fever and a severe anaemia (haemoglobin 3.7 g/dl). Macroscopical signs of inflammation with a severe diffuse friability were discovered by gastrointestinal endoscopy and histological analysis suggested a diagnosis of UC. He was treated with blood transfusion, antibiotics and steroid therapy without improvement. We then started a rescue therapy ciclosporin followed by mesalazine and azathioprine. His clinical history was characterized by relapsing symptoms and by the lack of response to drugs. In view of an IL10R mutations involvement, we analyzed the IL10R1 and IL10R2 mRNA of the proband and his parents, by using a combination of reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction. We observed a very lower level of IL10R1 mRNA expression in the proband of 0.1 fold change, compared to his father and mother that showed a value of 1 and 0.7 fold change respectively. No IL10R1 and IL10R2 mutations were found in any of the analyzed subjects. The SNPs analysis revealed that proband has homozygous G/G for SNPs rs.:2256111 and rs.:2229113 (located in a region responsible for receptor stability) and homozygous A/A for SNP rs.:9610, while his parents were both heterozygous A/G for these SNPs. In addition, the proband and his parents were heterozygous for the IL10RB K47E polymorphism, described to be associated with persistence of HBV infection and low level of IL10RB mRNA expression. Further studies are necessary to clarify the molecular mutations responsible for our patients disease; however, our data suggest that alterations of IL10R1 expression could be involved. It is possible that a specific SNPs haplotype contributes to disease manifestations with or without other mutations.

Cardiovascular disease (CVD) is the first cause of morbility and mortality among adults. The relationship between dyslipidemias, childhood overweight and high risk of premature CVD is well known. Current guidelines about management of dyslipidemias in children and adolescents, recommended a prudent diet which maintained adequate nutrients and calories and ideal body weight, while reducing the proportion of intake from total fat, saturated fat and cholesterol intake. Because of its presumed safety, lipid-lowering dietary therapy has been considered as the miliarstone of management. The safety about nutritional status of the fat and cholesterol restricted diet was investigated in various clinical trials. Childhood overweight is defined by a value of BMI from 85th to 95th percentile, while a value of BMI > 95th percentile is used to define obesity. Excess Body Weight (EBW%) is considered as the percentage of weight exceeding 50th centile and is used to estimate the degree of overweight. Objective: To evaluate the relationship between EBW and dyslipidemia in a cohort of dislipidemic children. Materials and methods: During a period of twenty-eight months, from January 2008 to April 2010, 382 outpatients (188 m and 194 f), aged from 1 to 18 yrs, were recruited at our Paediatric Lipid Unit. 246/382 were affected by familial hypercholesterolemia (FH), 9/382 by secondary hypercholesterolemia (SH), 3/382 by primary hypertrygliceridemia (PHT), 8/382 by secondary hypertrygliceridemia (SHT) and 116/382 hadn’t yet received a defined diagnosis. During this period of follow-up we estimated the EBW of our patients at the first visit, when children were in free diet. After they started a dietary program was evaluated the trend of weight at each control through analysis of EBW. Results: The mean value of EBW decreases from 111% (at the first visit) to 101,33% (at the last control) in patients with FH, from 126% to 111% in patients with SH, from 105,46% to 95,1% in patients with PHT, from 158,53% to 130,8% in patients with SHT while eraised from 112,98% to 129,21% in patients without a defined diagnosis. The graph below shows the trend of EBW for each group of patients.

Background and aim. In recent years the presence of antiendomysium EMA) and anti tissue transglutaminase 2 (anti-TG2) with a normal duodenal ucosa has been defined as potential coeliac disease (CD). Aim of our study as to characterise the natural history of potential CD. Patients.Two cohorts of children were recruited: 30 in the Pediatric Unit f Cava de’ Tirreni Hospital and 32 in the Department of Pediatrics at the niversity Federico II in Naples. Forty-two patients were Marsh T0 and 20 1. In all serum anti-TG2 and/or EMA were positive. All carried HLA DQ2 nd/or DQ8. The mean age was 6.7 years (range: 1.6–14.6). Methods. Growth and nutritional parameters, serology, autoimmunity, aecal calprotectin and intestinal permeability were assessed every 6 months. atients with persistent EMA and/or anti-TG2 even if not symptomatic were e-biopsied after 2 years. Results. The incidence of potential CD was 9.5–12%. Eight patients ere symptomatic and began a gluten-free diet. Symptoms resolved in 3/8 atients. All other patients had a normal daily gluten intake.13/62 potential D patients were first-degree relatives, 12/62 were affected by autoimmune iseases and 3/62 were asymptomatic. In all other cases gastrointestinal omplaints resolved with appropriate medical therapy. 33/54 patients entered the follow-up. After 2 years 17/33 patients were erologically negative, but two developed autoimmune disorders (diabetes, hyroiditis). During the follow-up biopsies were taken from 7 patients all MA and/or anti-TG2 positive. In 4 patients the second biopsy after 2 years nd in one patient the third biopsy after 5 years was still normal. Two patients eveloped partial villous atrophy, one at the second biopsy after 2 years and nother at the third biopsy after 5 years. Clinical and nutritional evaluation as normal in all patients except in one of the two patients who developed illous atrophy. In 9 patients we correlated faecal calprotectin, intestinal pereability and serology. Faecal calprotectin and intestinal permeability were ignificantly correlated (R= 0.71). Interestingly, in patients with positive MA and anti-TG2 >10 UA/ml (nv < 5) intestinal permeability and faecal alprotectin were abnormal; furthermore, these patients remained serologially positive during the follow-up and one developed partial villous atrophy. n patients with negative EMA and anti-TG2 < 10 intestinal permeability and aecal calprotectin were normal; during the follow-up they remained seroogically negative. Conclusions. Incidence of potential CD is increasing in the last years 3.8–17%). This condition is mainly seen in first-degree relatives (20%) and atients with autoimmune disorders (19%). In our cohort EMA and anti-TG2 eturned to normal in 50% of cases, but 6% developed other autoimmune iseases. Duodenal mucosa can remain normal for several years despite he presence of serum EMA and anti-TG2. Finally, the presence of both MA and anti-TG2 in addition to abnormal intestinal permeability, clinical ymptoms and faecal calprotectin seems to be strongly predictive of the volution to overt coeliac disease.