33 research outputs found
Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial
Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216-24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810-0.886]. For a cut-off value of </= 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods
Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study
8 páginas, 1 figura, 2 tablasCeliac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.This work was supported by grants AGL2011-25169, AGL2014-52101-P and AGL2007-66126-C03-03/ALI (YS and FP) from the Spanish Ministry of Economy and Competitiveness (MINECO). The scholarship to MO from CSIC (JAEpre) and the contract to ABP from the European Union's Seventh Framework Program under the grant agreement no 613979 (MyNewGut) are also fully acknowledged.Peer reviewe
Influence of Milk-Feeding Type and Genetic Risk of Developing Coeliac Disease on Intestinal Microbiota of Infants: The PROFICEL Study
Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder
Análisis genético y funcional de genes no HLA asociados a la enfermedad celÃaca
212 p. Figuras, tablas, bibliografÃa e ÃndiceEsta Tesis ha sido financiada por:
Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III.
Proyecto de Investigación PI020573
Consejo Superior de Investigaciones CientÃficas Ministerio de Educación y Ciencia
Proyecto Intramural de Frontera PROFICEL 200520F0092 y AGL2007-66126-C03-03
Consejo Superior de Investigaciones CientÃficas Ministerio de Ciencia e Innovación
Proyecto SAF2006-01147Peer reviewe
Planar cell polarity controls directional Notch signaling in the Drosophila leg
10 páginas, 8 figuras.The generation of functional structures during development requires tight spatial regulation of signaling pathways. Thus, in Drosophila legs, in which Notch pathway activity is required to specify joints, only cells distal to ligand-producing cells are capable of responding. Here, we show that the asymmetric distribution of planar cell polarity (PCP) proteins correlates with this spatial restriction of Notch activation. Frizzled and Dishevelled are enriched at distal sides of each cell and hence localize at the interface with ligand-expressing cells in the non-responding cells. Elimination of PCP gene function in cells proximal to ligand-expressing cells is sufficient to alleviate the repression, resulting in ectopic Notch activity and ectopic joint formation. Mutations that compromise a direct interaction between Dishevelled and Notch reduce the efficacy of repression. Likewise, increased Rab5 levels or dominant-negative Deltex can suppress the ectopic joints. Together, these results suggest that PCP coordinates the spatial activity of the Notch pathway by regulating endocytic trafficking of the receptorThis work was funded by a programme grant from the UK Medical Research Council [G0300034 to S.J.B.]; a Spanish Ministry of Science and Innovation project grant [BFU2009-07949 to M.I.G.]; and a ‘Ramón y Cajal’ fellowship [to M.I.G.]. M.B. is supported by a Spanish Research Council (CSIC) JAE-Tec contract.Peer reviewe
272 - Novel Intestinal Differentiation Approach from Human Induced Pluripotent Stem Cells for Modeling Hereditary Colorectal Cancer
Influence of breastfeeding versus formula feeding on lymphocyte subsets in infants at risk of coeliac disease: the PROFICEL study.
10 páginas.Purpose: In addition to genetic risk, environmental factors might influence celiac 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 breast-feeding (BF), and 91 partial breast-feeding 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 milkfeeding
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, 2881.23±973.48; BF, 2557.95±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. Breast-feeding might have a positive immunomodulatory effect on
lymphocyte subsets in infants at risk for CD.supported by grants AGL2007-66126-C03-01/ALI, AGL2007-66126-C03-02/ALI and
AGL2007-66126-C03-03/ALI, from the Spanish Ministry of Science and Innovation and grants
200570F0091 and 200570F0093 from CSIC.Peer reviewe
The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease
Objective: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. Design: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. Results: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). Conclusions: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.Peer Reviewe
Influence of early environmental factors on peripheral lymphocyte subsets and gut microbiota in infants at risk for celiac disease
Resumen del trabajo presentado al 6th International Workshop on Immunonutrition, celebrado del 15 al17 de octubre de 2012 en Palma de Mallorca.This work was supported by grants AGL2007-66126-C03-01/ALI and AGL2007-66126-C03-03/ALI from the Spanish Ministry of Science and Innovation.
T. Pozo-Rubio is recipient of a JAE-CSIC grant co-funded by European Social Fund