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Studies are scarce regarding IgG anti-tissue transglutaminase 2 (tTG) normalization in selective IgA deficient (SIgAD) celiac disease (CD) patients after beginning a gluten free diet (GFD). The aim of this study is to analyse the decreasing dynamics of IgG anti-tTG in patients diagnosed with CD who start a GFD. To achieve this objective, IgG and IgA anti-tTG levels at diagnosis and during follow-up in 11 SIgAD CD patients and in 20 IgA competent CD patients were retrospectively evaluated. At diagnosis, statistical differences were not found when comparing IgA anti-tTG levels of IgA competent subjects with IgG anti-tTG levels of SIgAD subjects. Regarding the decreasing dynamics, even though no statistical differences were found (p = 0.06), normalization rates were slower for SIgAD CD patients. After 1 and 2 years on GFD, respectively, only 18.2% and 36.3% of the SIgAD CD patients normalized IgG anti-tTG levels; otherwise, IgA anti-tTG reached values under the reference values in 30% and 80% of the IgA competent patients in the same time-points. Although IgG anti-tTG has demonstrated a high diagnostic efficiency in SIgAD CD pediatric patients, this test does not appear to be as precise for long-term GFD response monitoring as IgA anti-tTG levels in IgA sufficient patients. [ABSTRACT FROM AUTHOR]

Autologous cell replacement therapy for inherited metabolic disorders requires the correction of the underlying genetic mutation in patient's cells. An unexplored alternative for females affected from X-linked diseases is the clonal selection of cells randomly silencing the X-chromosome containing the mutant allele, without in vivo or ex vivo genome editing. In this report, we have isolated dermal fibroblasts from a female patient affected of ornithine transcarbamylase deficiency and obtained clones based on inactivation status of either maternally or paternally inherited X chromosome, followed by differentiation to hepatocytes. Hepatocyte-like cells derived from these clones display indistinct features characteristic of hepatocytes, but express either the mutant or wild type OTC allele depending on X-inactivation pattern. When clonally derived hepatocyte-like cells were transplanted into FRG® KO mice, they were able to colonize the liver and recapitulate OTC-dependent phenotype conditioned by X-chromosome inactivation pattern. This approach opens new strategies for cell therapy of X-linked metabolic diseases and experimental in vitro models for drug development for such diseases. [ABSTRACT FROM AUTHOR]

Summary: The association between low bone mineral density (BMD) and inflammatory bowel disease (IBD) is already known. Our study, performed in Spanish pediatric IBD patients at diagnosis onset, shows that low BMD already existed at the beginning of the disease. Low weight and height are also associated with low BMD and have to be considered as risk factors. Introduction: Inflammatory bowel disease (IBD) has been reported to be associated, even at disease onset, with low bone mass. The aim of this study was to know the bone mineral density (BMD) status in the IBD pediatric population of group of Spanish children, at the time of diagnosis. Material and methods: Retrospective review of patients' records from pediatric IBD patients diagnosed in our unit in the last 10 years. BMD was measured at the time of diagnosis and was expressed by Z-score. Results: Fifty-seven patients were included. Sixty-one percent were male and 47.4% had Crohn's disease (CD). Average age was 11.18 (SD 2.24) years old. Median BMD Z-score was − 0.30 (interquartile range: − 1.10 to + 0.10). Low BMD, defined as Z-score ≤ − 2SD, was present in 5% of patients, but there was no single patient with osteoporosis. There were no differences in BMD between Ulcerative Colitis (UC) and CD. Statistical differences appeared between healthy Spanish pediatric population and our IBD cohort, these having lower BMD for the same age and gender. A linear regression analysis showed a significant association between BMD Z-score and patient´s weight and height Z-score with a p values of 0.001 and 0.048, respectively. Conclusions: Suboptimal bone density is present at diagnosis in Spanish pediatric patients with IBD. There is no difference in BMD between patients with CD and UC. Lower weight and height are associated with a lower BMD; thus these data at IBD diagnosis should be considered as a risk factor for bone disease in the pediatric population. [ABSTRACT FROM AUTHOR]

Purpose: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. Methods: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. Results: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. Conclusion: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated. [ABSTRACT FROM AUTHOR]

Background/objectives: Gluten-free diet is the lifelong therapy for patients with coeliac disease. A wide range of gluten-free products (GFP) is available, which mimics the characteristics of their gluten-containing counterparts (GCC). The aim of this study was to compare the macronutrient and dietary fibre composition of GFP and GCC currently available in Spain.Subjects/methods: A cross-sectional study analysing the nutritional differences between 621 GFP and 600 GCC based on labelling information was conducted. Food items were categorized in one of 14 food groups. The first six ingredients were noted for each food item. A linear regression model was used to explain differences in nutritional composition between GFP and GCC and three independent models were created for bread, pasta and biscuits.Results: Results showed that GCC had higher protein content than GFP, especially in flour, bread, pasta and pizza. Bread had higher total and saturated fat contents in the GFP in which palm oil was the main fat used. Flours and starchy ingredients used in GFP formulation were mainly rice and corn flours and corn starch, and palm oil was the most commonly used fat.Conclusions: In conclusion, GFP cannot currently be considered as equivalent substitutes for their GCC. The reformulation of the GFP with more healthy ingredients and ingredients is encouraged, using a healthy oil, pseudocereals and whole flour. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND).Methods: 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit.Results: AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001).Conclusion: AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother’s diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers. [ABSTRACT FROM AUTHOR]

Purpose: In addition to genetic risk, environmental factors might influence coeliac disease (CD) development. We sought to assess the effect of the interaction between milk-feeding practices and the HLA-DQ genotype on peripheral lymphocyte subsets and their activation markers in infants at familial risk for CD. Methods: 170 newborns were classified in 3 different genetic risk groups (high risk, HR; intermediate risk, IR; and low risk, LR) after DQB1 and DQA1 typing. Lymphocyte subsets were studied at the age of 4 months by flow cytometry analysis. Results: 79 infants were receiving exclusive breastfeeding (BF) and 91 partial breastfeeding or formula feeding (FF). Regarding genetic risk, 40 infants were classified in HR group, 75 in IR group and 55 in LR group. Two-way ANOVA did not show significant interactions between the type of milk feeding and genetic risk group on the lymphocyte subsets analysed. One-way ANOVA for milk-feeding practice alone showed that the percentage of CD4 + CD25+ cells was significantly higher in BF group than in FF group (BF, 10.92 ± 2.71; FF, 9.94 ± 2.96; p = 0.026), and absolute counts of CD4 + CD38+ cells were significantly higher in FF group than in BF group (FF, 2,881.23 ± 973.48; BF, 2,557.95 ± 977.06; p = 0.038). One-way ANOVA for genetic risk alone showed that absolute counts of NK cells were significantly higher in IR group than HR and LR groups (IR, 539.24 ± 340.63; HR, 405.01 ± 239.53; LR, 419.86 ± 262.85; p = 0.028). Conclusion: Lymphocyte subset profiles in the early stages of life could be modulated by milk-feeding practices and genetic risk separately. Breastfeeding might have a positive immunomodulatory effect on lymphocyte subsets in infants at risk of CD. [ABSTRACT FROM AUTHOR]

Reference values of fecal calprotectin (fCP) have not been convincingly established in children. We aimed to investigate fCP concentrations in a larger population of healthy children aged 4–16 years to analyze more in depth the behavior of fCP in this age range and to determine if cut-off levels could be conclusively recommended. A prospective study was conducted to investigate fCP concentrations of healthy children aged 4–16 years. In 212 healthy children, the median and 95th percentile for fCP were 18.8 mg/kg and 104.5 mg/kg, respectively. We found a statistically significant association between the 95th percentile of fCP concentrations and age (p < 0.001). We propose a nomogram to facilitate the interpretation of fCP results in children aged 4–16 years. Further studies are required to validate the proposed values in clinical practice. [ABSTRACT FROM AUTHOR]