Serum antibodies and anthropometric data at diagnosis in pediatric Crohn's disease.
ABSTRACT Serum antibodies, including ASCA, anti-OmpC, and ANCA, correlate with disease location and predict disease phenotype in inflammatory bowel disease.
The objective of this study was to determine relationships between serum antibody status and anthropometric data for children with newly diagnosed Crohn's disease.
A retrospective review was conducted on children diagnosed with Crohn's disease at our institution from 2003 to 2008. Patients who had ASCA IgA, ASCA IgG, anti-OmpC, and pANCA antibodies, and anthropometric data measured before diagnosis and therapy were included. Z-scores for height and weight were compared among groups according to the presence of specific antibodies. Spearman's rank correlation was used to assess association between antibodies and growth data.
One hundred and two patients, mean age 11.9 years, met the inclusion criteria. Patients with the presence of any of the four antibodies had lower mean height and weight z-scores than patients without any antibodies present. When individual antibodies were studied, patients with positive ASCA titers had lower mean weight and height z-scores than patients without any antibodies present. Spearman's rank correlation coefficient demonstrated a significant association between increasing ASCA titers and lower weight z-scores, but not lower height z-scores.
Pediatric patients with newly diagnosed Crohn's disease and the presence of ASCA antibodies have lower mean height and weight z-scores. This study provides evidence that specific subsets of children with Crohn's disease may be at greater risk of growth impairment.
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ABSTRACT: Many Crohn's disease (CD) patients develop complications (fistulae and abscesses), and require surgery, often repeatedly and at variable instances. Identifying serological markers that determine their early or repeated manifestation can enable implementing more aggressive preventive strategies. Our objective was to study the ability of serological markers for predicting development of early (first) and recurrent complications or requirement for surgery. Serum anti-Saccharomyces cervisiae (ASCA) (IgA & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed close to diagnosis in a pediatric cohort of CD patients identified between 1996 and 1998. At diagnosis and follow-up, information was acquired on demographic and clinical features of disease. Relation between ASCA and clinical events was studied using adjusted Cox-proportional hazards modeling. The relative rates of recurrent clinical events according to the marker measures were compared. The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35 (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication, respectively. Time to occurrence of the first complication was lower among patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval (CI) = 0.99-5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI = 1.08-1.34). The rates of recurrent complications were higher among those positive or with higher ASCA titers. ASCA did not predict time to undergoing surgery independent of complications, and was unrelated to the occurrence of recurrent surgeries. Our study shows that serum ASCA measured close to diagnosis can determine the occurrence of early complications in pediatric CD. Preventive treatment targeted toward these susceptible patients could potentially modify the disease course.The American Journal of Gastroenterology 03/2006; 101(3):645-52. · 7.55 Impact Factor
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ABSTRACT: NOD2/CARD15 variants have recently been shown to be associated with Crohn's disease (CD). No analysis of NOD2/CARD15 gene variants has so far been reported in pediatric patients. Therefore, our aim was to analyze NOD2/CARD15 gene variants in children with CD and to perform genotype-phenotype analyses. We studied 101 children with CD and 136 healthy controls. Detailed phenotypic information was obtained from each patient. Patients were genotyped for the three NOD2/CARD15 variants R702W (single nucleotide polymorphism 8 [SNP8]), G908R (SNP12), and L1007fs (SNP13), and genotype-phenotype correlations were performed. We found 33 NOD2/CARD15 mutations in 29 of 101 patients (29%). The frequency of NOD2 variation was 31% in white (n=87) compared with 11% in controls (chi2=14; p=0.0001; OR=3.7; 95% CI=1.7-7.8). Four white patients but not control subjects were compound heterozygotes. NOD2/CARD15 variants were significantly associated with ileal disease (chi2=4.5; p=0.03; OR=5; 95% CI=0.9-35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile for weight at diagnosis, whereas only 15% of children without mutations were < or =5th percentile (chi2=8.7; p=0.003; OR=4.5; 95% CI=1.4-14.4). Similar trends were observed for height but they did not reach statistical significance. Our results demonstrate that: 1) the three NOD2/CARD15 variants confer risk to CD in children; 2) NOD2/CARD15 variants are associated with ileal disease in children as in adults; and 3) NOD2/CARD15 variants are associated with lower weight percentiles at diagnosis in children and a tendency toward lower height percentile, suggesting an association between growth in children with CD.The American Journal of Gastroenterology 11/2003; 98(11):2479-84. · 7.55 Impact Factor
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ABSTRACT: Genetic defects in genes encoding hormones, hormone receptors or polypeptides of the signaling pathways usually cause complex disease manifestations characterized by the involvement of several tissues and variable expression. Genetic aberrations, like chromosome aneuploidy, gene translocations or mutations in key regulatory proteins (even if not directly affecting genes of the endocrine system) often lead to clinical symptoms, including central endocrine functions like sexual differentiation or metabolic disturbances, like diabetes mellitus. But also minor genetic alterations like point mutations can affect the function of gene products to cause endocrine diseases. If the underlying molecular defects of endocrinopathies are known, direct molecular diagnosis can be performed. This is particularly useful if it helps to solve difficult differential diagnosis problems or if there exist effective preventive therapeutic options. The present paper presents examples for endocrine diseases in which molecular testing significantly increases the specificity and sensitivity of diagnostics and demonstrates the benefits for the patients and the healthcare system. In multiple endocrine neoplasia type 2, an unambiguous identification of gene carriers in affected families can be achieved by genetic testing. As a preventive measure to avoid medullary thyroid carcinoma, prophylactic thyroidectomy is recommended for individuals carrying the disease causing mutation. In adrenogenital syndrome, sequence analysis of the steroid 21-hydroxylase gene has become an important tool to confirm or exclude suspected late-onset forms of the disease, where hormone measurements are not informative. The major benefit, however, lies in identifying heterozygous carriers and providing a reliable prenatal test for couples carrying a defect in the 21-hydroxylase gene. Today, prenatal treatment with dexamethasone, which prevents the virilization in female fetuses, should always be based on results from molecular diagnosis performed from chorionic villus samples.Hormone Research 02/2002; 58 Suppl 3:7-15. · 2.48 Impact Factor