Additional value of serum I-FABP levels for evaluating celiac disease activity in children.
ABSTRACT Addition of a non-invasive marker for intestinal damage to the currently used parameters for celiac disease activity (symptoms, serologic tests and biopsy) might further improve clinical management of celiac disease (CD). Intestinal fatty acid binding protein (I-FABP) is a cytosolic enterocyte protein and sensitive marker for enterocyte damage in the small intestine. We investigated whether serum I-FABP levels can reliably identify villous atrophy in children with a positive CD antibody screening. Moreover, the recovery of I-FABP levels after gluten free diet (GFD) was studied.
I-FABP levels were analyzed retrospectively in 49 children with biopsy proven CD and in 19 patients with a positive screening but without histological confirmation of CD. Blood was collected before biopsy and repeatedly after the onset of GFD.
Initial I-FABP concentrations in CD (median 458 pg/ml) were significantly (p < 0.001) elevated compared to controls (median 20 pg/ml). In the control group, only two of 19 children were found to have elevated I-FABP levels, of which one was subsequently diagnosed with CD after gluten challenge. I-FABP concentrations correlated with severity of villous atrophy. In all CD patients, I-FABP levels decreased quickly after GFD and normalized in 80% of patients within 12 weeks.
Elevated I-FABP levels accurately predict villous atrophy in children with a positive serologic test for CD (positive predictive value 98%). In addition, measurement of I-FABP enables monitoring the response to GFD.
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ABSTRACT: Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects. All samples were also analyzed for anti-endomysium antibodies (EMA). The levels of IgA and IgG anti-tTG antibodies correlated with the condition of the small intestinal villous structure and the serum levels of IgA EMA. All of the 25 serum samples obtained from untreated patients contained IgA anti-tTG antibodies, and 24 of 25 also had IgA EMA. Of the serum samples from 53 control children, two had IgA anti-tTG antibodies and two had IgA EMA. Children younger than 5 y of age with untreated celiac disease had the highest serum levels of both IgA and IgG anti-tTG. There was already an increase in IgA anti-tTG antibodies after 2 wk of gluten challenge (p < 0.01). Although the criteria-based diagnosis of childhood celiac disease still depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides useful complementary diagnostic information. The human recombinant tTG-based ELISA can be used as a sensitive and specific test to support the diagnosis and may also be used in the follow-up of treatment in childhood celiac disease.Pediatric Research 06/2002; 51(6):700-5. · 2.67 Impact Factor
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ABSTRACT: The development of sepsis and multiple organ failure are important determinants of the outcome in critically ill patients. Hepatosplanchnic hypoperfusion and resulting intestinal and hepatic cell damage have been implicated as central events in the development of sepsis and multiple organ failure. Our aim was to study (1) the relation between intramucosal perfusion and intestinal and hepatic cell damage in an early phase of sepsis and (2) the correlation of these parameters with mortality. Two groups of patients were consecutively selected after intensive care unit admission: patients with postoperative abdominal sepsis (n = 19) and patients with pneumonia-induced sepsis (n = 9). Intramucosal perfusion was assessed by gastric tonometry (Pr-aCO2 gap, Pico2). Circulating levels of intestinal fatty acid binding protein (I-FABP) and liver (L)-FABP were used as markers for intestinal and hepatic cellular damage, respectively. Outcome was determined on day 28. Pr-aCO2 gap correlated with I-FABP (Pearson r = 0.56; P < 0.001) in all patients, and gastric mucosal Pico2 correlated significantly with I-FABP (r = 0.57; P = 0.001) in patients with abdominal sepsis. At intensive care unit admission, nonsurvivors had significantly higher I-FABP and L-FABP values than survivors (I-FABP: 325 vs. 76 pg/mL, P < 0.04; L-FABP: 104 vs. 31 ng/mL, P < 0.04). Patients with abdominal sepsis was especially responsible for high-admission I-FABP and L-FABP levels in nonsurvivors (I-FABP: 405 vs. 85 pg/mL, P < 0.04; L-FABP: 121 vs. 59 ng/mL, P < 0.04). This study shows that splanchnic hypoperfusion correlates with intestinal mucosal damage, and that elevated plasma levels of I-FABP and L-FABP are associated with a poor outcome in critically ill patients with abdominal sepsis.Shock 11/2007; 28(5):544-8. · 2.61 Impact Factor
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ABSTRACT: The natural history of the appearance and fate of transglutaminase autoantibodies (TGAs) and mucosal changes in children carrying HLA-conferred celiac disease (CD) risk remains obscure. The aim of this study was to investigate the sequence of events leading to overt CD by retrospective analysis of TGA values in serum samples collected frequently from genetically susceptible children since birth or early childhood. A total of 1101 at-risk children were recruited in the study. A duodenal biopsy was recommended to all TGA-positive children and performed if parental consent was obtained. During up to 8 years of follow-up, 35 of the cohort children developed TGAs, the youngest at age 1.3 years. After age 1.3 years the annual TGA seroconversion rate was constantly around 1% at least until age 6 years. However, 18 of the 35 TGA-positive children (51%) lost TGAs, without any dietary manipulation. A further 7 children were IgA deficient; of these children, 2 developed IgG antigliadin antibodies (IgG-AGA). Only 13 of the 21 children (62%) who had duodenal biopsies had villous atrophy. The time that passed since emergence of TGAs failed to predict the biopsy findings. Only one of the children with TGAs and both of the IgA-deficient children with IgG-AGA had noticeable abdominal symptoms. TGAs appear in children at a constant rate after 1 year of age until at least the age of 6 years. Over half of the children loose TGA without gluten exclusion, challenging TGA positivity-based CD prevalence estimates. In symptom-free children, a requirement of two consecutive TGA-positive samples taken >or=3 months apart before performing a duodenal biopsy might diminish the number of unnecessary intestinal biopsies.Scandinavian Journal of Gastroenterology 10/2005; 40(10):1182-91. · 2.16 Impact Factor