Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients.

We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants.

Activating Killer-cell Immunoglobulin-like Receptor genes confer risk for Crohn's disease in children and adults of the Western European descent: Findings based on case-control studies.

Background: Killer-cell Immunoglobulin-like Receptor (KIR) genes encode receptors, which are mainly expressed on, and control functional activities of, Natural Killer (NK) cells. There exist six distinct activating KIR genes in humans, who differ from one another with respect to the repertoire of these genes. Because activated NK cells can potentially cause tissue destruction, we hypothesized that variation in the inherited activating KIR genes in humans is associated with their innate susceptibility/resistance to developing Crohn disease (CD).

Parental occupations and risk for Crohn's disease in children.

Background And Objectives: Lacunae exist on the identity of specific environmental risk factors that associate with Crohn's disease (CD). We hypothesized that indirect exposures acquired via the parents' occupation may confer susceptibility.

Methods: A case-control study based on children diagnosed with CD (prior to age 20) at a tertiary care gastroenterology clinic in Montreal, Canada was carried out.

Steroid Administration and Growth Impairment in Children with Crohn's Disease.

Background: Growth impairment remains a major concern in children with Crohn's disease, but evidence remains unclear, in particular, whether steroid use is implicated. We aimed to (1) determine the frequency of temporary (TGI) and permanent (PGI) growth impairment in children administered steroids and (2) examine whether cumulative steroid administration was associated with TGI and/or PGI.

Methods: A retrospective cohort study was performed in patients with Crohn's disease (<18 yr) administered steroids at the gastroenterology clinics of Sainte-Justine Hospital, Montreal.

Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease.

Increased dietary ratios of ω6/ω3 polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease (CD), but epidemiologic data are limited. We investigated whether variants of genes that control polyunsaturated fatty acid metabolism (CYP4F3, FADS1, and FADS2), along with the dietary ratio of ω6/ω3, confers susceptibility to CD. Based on data from 182 children newly diagnosed with CD and 250 controls, we found that children who consumed a higher dietary ratio of ω6/ω3 were susceptible for CD if they were also carriers of specific variants of CYP4F3 and FADS2 genes.

Genome-wide association study signal at the 12q12 locus for Crohn's disease may represent associations with the MUC19 gene.

Background: Genome-wide association studies (GWAS) in Crohn's disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes.

Methods: We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case-control sample comprising CD cases aged <18 years at diagnosis.

A non-synonymous coding variant (L616F) in the TLR5 gene is potentially associated with Crohn's disease and influences responses to bacterial flagellin.

Background And Objectives: Although numerous studies have implicated TLR5, or its ligands, bacterial flagellins, in the pathogenesis of Crohn's disease (CD), genome-wide association studies (GWAS) have not reported associations with the TLR5 gene. We aimed to examine potential CD-associated TLR5 variants and assess whether they modified inflammatory responses to bacterial flagellins.

Methods And Principal Results: A two-stage study was carried out.

Association between the PTPN2 gene and Crohn's disease: dissection of potential causal variants.

Background: Although genome-wide association studies (GWAS) and subsequent meta-analyses have confirmed associations between the PTPN2 (protein tyrosine phosphatase, nonreceptor type 2) gene and Crohn's disease (CD), the potential causal variants remain unidentified. We aimed to dissect potential causal CD-associated PTPN2 variants, assess their functional significance, and relate PTPN2 protein expression with inflammation in CD.

Methods: A 3-stage study was carried out.

Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease.

The exogenous triggers responsible for Crohn's disease (CD) relapses are not often identified. Cytomegalovirus and other members of the herpesvirus family have been implicated in precipitating relapses. However, the role of viral infections in the immunopathogenesis of CD remains poorly understood.

Variation in the glucocorticoid receptor gene (NR3C1) may be associated with corticosteroid dependency and resistance in children with Crohn's disease.

Objectives: In pediatric onset of Crohn's disease (CD), corticosteroid dependency (approximately 40%) and resistance (approximately 10%) are significant clinical problems. Given the known effects of the glucocorticoid receptor (GR/NR3C1) gene in corticosteroid metabolism, we investigated whether variation in the gene was associated with corticosteroid response.

Methods: A retrospective cohort study was carried out including patients with CD diagnosed before 18 years and treated with a first course of corticosteroids in two Canadian tertiary pediatric gastroenterology clinics.

Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia.

Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest.

NELL1, NCF4, and FAM92B genes are not major susceptibility genes for Crohn's disease in Canadian children and young adults.

Background: Genome-wide association studies (GWAS) and replication studies have shown conflicting associations between the NELL1, NCF4, and FAM92B genes and susceptibility for Crohn's disease (CD). We sought to examine whether these genes were associated with CD in Canadian children and young adults.

Methods: A case-control study was carried out at three pediatric gastroenterology clinics across Canada.

Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn's disease in children & young adults.

Background And Objectives: Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD.

Methods And Principal Results: A case-control design was implemented at three pediatric gastroenterology clinics in Canada.

Immediate and long-term outcomes of corticosteroid therapy in pediatric Crohn's disease patients.

Background: Although a mainstay of treatment of moderate to severe Crohn's disease (CD), corticosteroids use presents significant challenges because of large interindividual variability in response. Corticosteroid-dependence is of particular concern in children, where high rates have been reported. We examined the burden of corticosteroid-resistance and dependence in a well-characterized cohort of pediatric CD patients and investigated potential predictors of response.

Association between genome-wide association studies reported SNPs and pediatric-onset Crohn's disease in Canadian children.

A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn' disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case-control design was implemented at three pediatric gastroenterology clinics in Canada.

Investigation of reported associations between the 20q13 and 21q22 loci and pediatric-onset Crohn's disease in Canadian children.

Objectives: A recent pediatric-focused genome-wide association study has reported novel associations of the 20q13 and 21q22 loci with inflammatory bowel disease (IBD). We aimed to investigate these associations with Crohn's disease (CD) in Canadian children.

Methods: A combined case-control and case-parent design was implemented at three pediatric gastroenterology clinics in Canada.

Associations between ABCB1/MDR1 gene polymorphisms and Crohn's disease: a gene-wide study in a pediatric population.

Background: Functional studies support the involvement of the MDR1 gene in the pathways leading to Crohn's disease (CD). Two common single nucleotide polymorphisms (SNPs), C3435T and G2677T/A, thought to alter the function of the corresponding P-glycoprotein, have shown inconsistent associations with CD. We investigated whether DNA variants in the MDR1 gene were associated with susceptibility for CD and specific phenotypes in children.

Autophagy gene ATG16L1 but not IRGM is associated with Crohn's disease in Canadian children.

Background: Recent genome-wide studies have implicated the autophagy genes ATG16L1 and IRGM in the pathogenesis of Crohn's disease (CD). We investigated whether these genes were associated with CD in Canadian children.

Methods: A case-control study was carried out at 2 pediatric gastroenterology clinics in Canada.

Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome.

Objective: To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS).

Design: Prospective cohort study.

Setting: Tertiary care, university-affiliated pediatric intensive care unit (PICU).

Investigation of associations between the pregnane-X receptor gene (NR1I2) and Crohn's disease in Canadian children using a gene-wide haplotype-based approach.

Background: The pregnane-X-receptor (PXR) is involved in the metabolism and detoxification of numerous xenobiotics and is critical for maintaining intestinal integrity. The NR1I2 gene encoding PXR may confer susceptibility for Crohn's disease (CD) but evidence for associations is conflicting. We investigated whether the NR1I2 gene was associated with susceptibility for pediatric CD.

Dietary patterns and risk for Crohn's disease in children.

Background: Some dietary foods are considered protective (vegetables and fruits), whereas others (fatty foods) are thought to enhance the risk for Crohn's disease (CD). The evidence, however, is inconsistent.

Methods: We postulated that specific dietary patterns may influence the risk for CD.

Association between genetic variants in the IL-23R gene and early-onset Crohn's disease: results from a case-control and family-based study among Canadian children.

Background And Objectives: Interleukin (IL)-23 is a key regulator of inflammation and influences the activities of T-helper 17 (Th-17) lymphocytes. Recent reports indicate that variants in the gene coding for its receptor (IL-23R) are strongly associated with Crohn's disease (CD). We investigated whether DNA variants in the IL-23R gene determine susceptibility for CD in Canadian children.

Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn's disease in children.

Background And Objectives: The role of dietary factors in the etiology of Crohn's disease (CD) is inconsistent largely due to difficulties in acquiring valid information on consumption habits. We examined the impact of diet on new onset CD in children using a validated food-frequency questionnaire (FFQ).

Methodology: A case-control study was carried out.

Temporal changes in rates of stillbirth, neonatal and infant mortality among triplet gestations in the United States.

Objective: The purpose of this study was to examine temporal changes in stillbirth, neonatal and infant mortality rates among triplet births in the US, and to assess the contributions of triplet delivery at < 34 weeks to these changes.

Study Design: Data on triplet live births, and fetal and infant deaths (1990-2002) delivered at > or = 22 weeks and fetuses weighing > or = 500 g (n = 66,986) were derived from the US linked birth/infant death data files. Relative risk (RR), quantifying changes in triplet stillbirth, neonatal (death within the first 28 days) and infant mortality (death within the first year) rates between 1990 and 1991 and 2001 and 2002, were derived.