Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset.

PURPOSE:We present a case-control study of seven polymorphisms of six genes involved in homocysteine/folate pathway as risk factors for Down syndrome. Gene-gene/allele-allele interactions, haplotype analysis and the association with age at conception were also evaluated. METHODS: We investigated 94 Down syndrome-mothers and 264 control-women from Campania, Italy. RESULTS: Increased risk of Down syndrome was associated with the methylenetetrahydrofolate reductase (MTHFR) 1298C allele (OR 1.46; 95% CI 1.02-2.10), the MTHFR 1298CC genotype (OR 2.29; 95% CI 1.06 -4.96), the reduced-folate-carrier1 (RFC1) 80G allele (1.48; 95% CI 1.05-2.10) and the RFC1 80 GG genotype (OR 2.05; 95% CI 1.03-4.07). Significant associations were found between maternal age at conception Ն34 years and either the MTHFR 1298C or the RFC 180G alleles. Positive interactions were found for the following genotype-pairs: MTHFR 677TT and 1298CC/CA, 1298CC/CA and RFC1 80 GG/GA, RFC1 80 GG and methylenetetrahydrofolate-dehydrogenase 1958 AA. The 677-1298 T-C haplotype at the MTHFR locus was also a risk factor for Down syndrome (P ϭ 0.0022). The methionine-synthase-reductase A66G, the methionine-synthase A2756G and the cystathionine-beta-synthase 844ins68 polymorphisms were not associated with increased risk of Down syndrome. CONCLUSION: These results point to a role of maternal polymorphisms of homocysteine/folate pathway as risk factors for Down syndrome. Genet Med 2006:8(7):409-416.

W e read with interest the recent report by Haustein et al entitled "The likelihood of an indeterminate test result from a whole-blood interferon-␥ release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status." 1 This report adds to recent publications that question the performance of current interferon-␥ (IFN-␥) release assays (IGRA) for the diagnosis of tuberculosis (TB) in routine pediatric clinical practice. [2][3][4][5][6] The retrospective study by Haustein et al in 237 children highlights the high proportion of indeterminate test results ob-tained with the QuantiFERON-TB (QFT) Gold In-Tube assay (35% of the study population). Notably, indeterminate test results were over-represented in children younger than 5 years of age, and those with immunodeficiencies or medical conditions associated with immunosuppression. Importantly, these groups represent children most at risk for disease progression after exposure to M. tuberculosis. FIGURE 1.A, Relationship between PHA mitogen (positive) control response (censored at 15 IU/mL) and age with fitted linear regression line; (B) PHA mitogen control responses stratified by age (bars represent median values; P values were calculated by Mann-Whitney U test); (C) Proportion of indeterminate QFT assay results (ie, assays with failed PHA mitogen control response and/or high nil (negative) control combined) stratified by age ( 2 test).

Background Hyperbilirubinemia can lead to potentially irreversible bilirubin-induced neurotoxicity. Transcutaneous bilirubin (TcB) determination has become a valuable aid in non invasive screening of neonatal jaundice. The aim of this study is to compare the performance of three most widespread transcutaneous bilirubinometers on a multiracial population of term and late pre-term neonates. Methods Bilirubin concentration was determined using traditional photometric determination and transcutaneously with Bilicheck, BiliMed and JM-103, in random order. Total serum bilirubin (TSB) was determined over a wide concentration range (15,8–0,7 mg/dl) with a mean of 9,5 mg/dl. Related TcB values using Bilicheck (TcB-BC), BiliMed (TcB-BM), and JM-103 (TcB-JM) are reported in Table 1. Results A multiracial population of 289 neonates was enrolled with a gestational age ranging from 35 to 41 weeks; birth weight ranging from 1800to 4350 grams; hours of life ranging from 4 to 424. In the total study population correlation analysis using Pearson coefficients showed good results for Bilicheck (r = 0.86) and JM-103 (r = 0.85) but poor for BiliMed (r = 0,70). Similar results were found for the non-Caucasian neonates subgroup. Bilicheck and JM-103 had a greater area under the curve than BiliMed when TSB =14 mg/dl was chosen as a threshold value both for the total study population and the non-Caucasian subgroup. Conclusions Bilicheck and JM-103, but not BiliMed, are equally reliable screening tools for hyperbilirubinemia in our multiracial neonatal population.

In our population of VLBW IUGR newborns with severe feeding intolerance, a short course on AAF was a safe and effective means of nutritional rescue.