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.

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.

In children, aplastic anemia (AA) is a common complication associated with fulminant hepatic failure (FHF). The objective of this study was to determine whether specific pretransplantation clinical and laboratory characteristics can be used to distinguish between patients with FHF who are at higher risk of developing AA. We performed a retrospective casecontrol study to evaluate the clinical and laboratory characteristics of those patients who presented with evidence of FHF and eventually developed aplastic anemia. We identified nine patients with AA, and all had the indeterminate form of FHF and underwent liver transplantation (LTx). The AA patients were compared with a control group of 47 patients with indeterminate FHF that underwent transplantation and did not develop AA. We found that males were over-represented in the group of patients that developed AA (p = 0.01). Furthermore, during the pretransplant period, the AA group had a significantly lower white count (p = 0.005), absolute lymphocyte count (p = 0.004), and platelet count (p = 0.019) when compared with controls. We conclude that evidence of early bone marrow dysfunction is apparent before liver transplantation and the development of AA in a subset of patients with the indeterminate form of FHF.

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Background: Although IgA endomysial antibodies (EMA) and tissue transglutaminase (TG) are sensitive and specific serologic tests for the diagnosis of celiac disease, there is limited information on the association of the magnitude of antibody level with the severity of the histological abnormalities of the intestine. Purpose: To determine if EMA and TG titers correlate with the severity of histological changes in patients with celiac disease. Methods: We identified 148 children from our laboratory database that had EMA, TG and intestinal biopsies performed. IgA EMA was determined by indirect immunofluorescence with results expressed as a dilutional titer with positivity determined at 1:5. IgA TG was determined by an enzyme linked human immunosorbent ELISA assay with results expressed in standardized units. A modified Marsh histological grading system was used to describe the duodenal biopsies: Type 0 normal, I increased intraepithelial lymphocytes (IEL), II hyperplastic crypts, IIIa partial villus atrophy, IIIb subtotal villus atrophy, IIIc total villous atrophy. Results: Mean values for EMA (Table 1) and TG (Table 2) progressively increased with increasing Marsh score. Conclusion:There was considerable variability in EMA and TG levels for each Marsh grade, so that an individual level could not be utilized to predict histological severity. The data show that as a group, increasing severity of the histological lesion in celiac disease was associated with increased levels of both IgA EMA and TG antibodies.