Background and Aim The ability to identify children with Crohn’s disease who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. Aim: To determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression. Methods Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C (anti-OmpC), anti-Saccharomyces-cerevisiae (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA) using ELISA. Genotyping (TaqmanMGB) was performed for 3 CARD15 variants (SNPs 8, 12, 13). Associations between immune responses (antibody sum (AS) and quartile sum score (QSS), CARD15, and clinical phenotype were evaluated. Results 32% of patients developed at least one disease complication within a median of 32 months and 18% underwent surgery. The frequency of internal penetrating (IP), stricturing (S) and surgery significantly increased (p trend < 0.0001 for all 3 outcomes) with increasing AS and QSS. 9% of seropositive groups had IP/S vs. 2.9% in the seronegative group (p=0.01). 12% of seropositive groups underwent surgery vs. 2% in the seronegative group (p=0.0001). The highest AS group (3) and QSS group (4) demonstrated the most rapid disease progression (p < 0.0001). Increased hazard ratio was observed for AS group 3 (7.8 [2.2–28.7] p < 0.002 and QSS group 4 (11.0 [1.5,83.0] p < 0.02). Conclusions The rate of complicated CD increases in children as the number and magnitude of immune reactivity increases. Disease progression is significantly faster in children expressing immune reactivity.

The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

Background-The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients.

BACKGROUND-Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy.

Direct all correspondence to: James Markowitz, MD, Schneider Children's Hospital, 269-01 76 Ave, New Hyde Park, NY 11040, Phone: 718-470-3430, Fax: 718-962-2908 Crohn disease (CD) is often associated with antibodies to microbial antigens. Differences in immune response may offer clues to the pathogenesis of the disease.AIM-To examine the influence of age at diagnosis on serologic response in children with CD.METHODS-Data were drawn from 3 North American multicenter pediatric IBD research consortia. At or shortly after diagnosis, pANCA, ASCA IgA, ASCA IgG, anti-ompC and antiCBir1 were assayed. Results were compared as a function of age at CD diagnosis (0-7 years vs 8-15 years).RESULTS-705 children (79 <8 yr of age at diagnosis, 626 ≥8yr) were studied. Small bowel CD was less frequent in the younger group (48.7% vs 72.6%; p<0.0001) while colonic involvement was comparable (91.0% vs 86.5%). ASCA IgA and IgG were seen in <20% of those 0-7 yr compared to nearly 40% of those 8-15 yr (p<0.001), while anti-CBir1 was more frequent in the younger children (66% vs 54%, p<0.05). Anti-CBir1 detected a significant number of children in both age groups who otherwise were serologically negative. Both age at diagnosis and site of CD involvement were independently associated with expression of ASCA and anti-CBir1.CONCLUSIONS-Compared to children 8-15 yr of age at diagnosis, those 0-7 yr are more likely to express anti-CBir1 but only half as likely to express ASCA. These age-associated differences in antimicrobial seropositivity suggest that there may be different, and as yet unrecognized, genetic, immunologic and/or microbial factors leading to CD in the youngest children.

ABSTRACT. We studied the effects of a diet that was low in fat, high in carbohydrate (CHO) on milk lipid composition and de novo endogenous fatty acid synthesis by the mammary gland in five lactating women. The women consumed either a low fat (LF) (5% fat, 80% CHO) diet or a high fat (HF) (40% fat, 45% CHO) diet. Fat synthesis was determined after an oral dose of 500 mg/kg DzO by measuring the incorporation of deuterium into C10:O to C18:O saturated fatty acids of milk fat and plasma triglycerides by gas chromatography-mass spectrometry. Synthesis of plasma C16:O and C18:O triglycerides was barely detectable while women consumed the H F diet, but was increased 6-fold during the LF diet. Medium chain fatty acids secreted by the mammary gland increased from 12.8% (HF diet) to 16.3% (LF diet) in milk fat from four of five subjects ( p = 0.027). Medium chain fatty acid secretion, however, increased from 13.9% (HF diet) to 29.9% (LF diet) in one subject. The primary fatty acids synthesized during lactation were C10:0, C12:0, and C14:O in the majority of women studied. The LF diet significantly increased the apparent synthesis of C14:O ( p = 0.05), whereas no changes were observed in C12:0, C16:0, or C18:O. One subject had highly enriched C16:O and C18:O fatty acids in her milk on the LF diet, which could have been the result of mammary synthesis or of transport and secretion of hepatically synthesized lipids. (Pediatr Res 25:63-68,1989) Abbreviations CHO, carbohydrate LF, low fat HF, high fat FA, fatty acids FAME, fatty acid methyl esters GC-MS, gas chromatography-mass spectrometry ApoB, apolipoprotein B TG, triglycerides MCT, medium chain triglycerides (C10, C12, C14) CM, chylomicrons VLDL, very low density lipoproteins Milk lipid is comprised of 98% TG, 1% phospholipid, and 0.5% cholesterol and cholesterol ester, and provides 50 to 60% of an infant's energy intake (1). Milk TG contain FA derived from three sources: de novo mammary synthesis, dietary lipids, and mobilized adipose or hepatic lipids (2). Variations in the FA intake and composition of the mother's diet are known to alter the FA composition of her milk (3); for example, a LF, high CHO diet increased proportions of C10:O, C12:0, and C14:O FA whereas the proportion of C16 and C18 FA was reduced (4-6). This diet, however, did not change total milk fat content significantly, and these studies were unable to distinguish between altered mammary synthesis, changes in whole body lipogenesis, and lipid transport induced by the high CHO diet.The incorporation of deuterium into cholesterol and FA during lipogenesis was first demonstrated in the classic work of Rittenberg and Schoenheimer (7), and 22 of 31 protons in palmitic acid are known to be derived from body water (8). Despite the widespread use of deuterium to measure total body water (9), it has not been applied to the systematic study of lipogenesis in humans.Isotopic tracers are required to distinguish between FA synthesized de novo by the body and those of dietary origin. We have described the use o...

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TM may be effective in promoting adherence in children with IBD. Larger and longer multicenter studies are required to confirm this finding.