Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies
ABSTRACT BACKGROUND: Enterocyte damage is the hallmark of coeliac disease (CD) resulting in malabsorption. Little is known about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a sensitive marker to study enterocyte damage. AIMS: To evaluate the severity of enterocyte damage in adult-onset CD and its course upon a gluten-free diet (GFD). Furthermore, the correlation among enterocyte damage, CD autoantibodies and histological abnormalities during the course of disease is studied. METHODS: Serum I-FABP levels were determined in 96 biopsy-proven adult CD patients and in 69 patients repeatedly upon a GFD. A total of 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels served as controls. I-FABP levels were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. RESULTS: I-FABP levels were elevated in untreated CD (median 691 pg/mL) compared with controls (median 178 pg/mL, P < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). Upon a GFD serum levels decreased significantly, however, not within the range observed in controls, despite the common observed normalisation of IgA-tTG levels and Marsh grade. CD patients with elevated I-FABP levels nonresponding to GFD showed persistent histological abnormalities. CONCLUSIONS: Enterocyte damage assessed by serum I-FABP correlates with the severity of villous atrophy in coeliac disease at the time of diagnosis. Although enterocyte damage improves upon treatment, substantial enterocyte damage persists despite absence of villous atrophy and low IgA-tTG levels in the majority of cases. Elevated I-FABP levels nonresponding to gluten-free diet are indicative of histological abnormalities and warrant further evaluation.
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ABSTRACT: OBJECTIVES:: : To examine the impact of Serum-derived Bovine Immunoglobulin, an oral medical food known to neutralized bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal (GI) function in subjects with HIV enteropathy. DESIGN:: : Open-label trial with intensive 8-week phase of SBI 2.5 grams twice daily with a 4-week wash-out period and an optional 9-month extension study. METHODS:: : HIV enteropathy was defined as chronic GI symptoms including frequent loose or watery stools despite no identifiable, reversible etiology. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed pre- and post-8 weeks of SBI to test mucosal immunity and GI function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated GI questionnaire assessed changes in symptoms. RESULTS:: : All eight subjects experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention but D-xylose absorption increased in 7/8 subjects. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm from 213 to 322 cells/mm (P = 0.016). Intestinal-Fatty Acid Binding Protein (I-FABP), a marker of enterocyte damage, initially rose in 7/8 subjects after 8 weeks (P = 0.039), and then fell below baseline in 4/5 who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046). CONCLUSIONS:: : SBI significantly increases intestinal mucosal CD4 lymphocyte counts, function, and showed evidence of intestinal repair in the setting of HIV enteropathy.AIDS (London, England) 05/2013; 27(14). DOI:10.1097/QAD.0b013e328362e54c · 6.56 Impact Factor
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ABSTRACT: Background. Microbial translocation has been implicated in the pathogenesis of liver fibrosis and cirrhosis. We sought to determine if markers of microbial translocation are associated with liver disease progression in HIV/hepatitis C (HCV) co-infection.Methods. We measured serial plasma lipopolysaccharide (LPS), EndoCAb, intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), IL-6, IL-10 and TNF-α over a five year period in 44 HIV/HCV co-infected women, comparing 21 women who experienced liver disease progression to 23 non-progressors.Results. While LPS levels did not differ significantly over time between progressors and non-progressors (p=0.60), progressors had significantly higher plasma sCD14, a marker of monocyte activation by LPS, at the first timepoint measured (p=0.03) and throughout (p=0.001); Progressors also had higher IL-6 levels and I-FABP over the five year study period (p=0.02 and 0.03 respectively). The associations between progression and sCD14, I-FABP and IL-6 were unchanged in models controlling for HIV RNA and CD4 cell count.Conclusion. Although LPS did not differ between liver disease progressors and non-progressors, the association of sCD14, I-FABP and IL-6 with liver disease progression suggests that impairment of gut epithelial integrity and consequent microbial translocation may play a role in the complex interaction of HIV and hepatitis C pathogenesis.The Journal of Infectious Diseases 05/2013; 208(4). DOI:10.1093/infdis/jit225 · 5.78 Impact Factor
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ABSTRACT: OBJECTIVES:Histological examination of duodenal biopsies is the gold standard for assessing intestinal damage in celiac disease (CD). A noninvasive marker of disease status is necessary, because obtaining duodenal biopsies is invasive and not suitable for routine monitoring of CD patients. As the small intestine is a major site of cytochrome P450 3A4 (CYP3A4) activity and also the location of the celiac lesion, we investigated whether patients with active CD display abnormal pharmacokinetics of an orally administered CYP3A4 substrate, simvastatin (SV), which could potentially be used for noninvasive assessment of their small intestinal health.METHODS:Preclinical experiments were performed in CYP3A4-humanized mice to examine the feasibility of the test. Subsequently, a clinical trial was undertaken with 11 healthy volunteers, 18 newly diagnosed patients with CD, and 25 celiac patients who had followed a gluten-free diet (GFD) for more than 1 year. The maximum concentration (Cmax) of orally administered SV plus its major non-CYP3A4-derived metabolite SV acid (SV equivalent (SVeq)) was measured, and compared with clinical, histological, and serological parameters.RESULTS:In CYP3A4-humanized mice, a marked decrease in SV metabolism was observed in response to enteropathy. In the clinical setting, untreated celiac patients displayed a significantly higher SVeq Cmax (46±24 nM) compared with treated patients (21±16 nM, P<0.001) or healthy subjects (19±11 nM, P<0.005). SVeq Cmax correctly predicted the diagnosis in 16/18 untreated celiac patients, and also the recovery status of all follow-up patients that exhibited normal or near-normal biopsies (Marsh 0-2). All patients with abnormal SVeq Cmax showed a reduction in the value after 1 year of following a GFD.CONCLUSIONS:SVeq Cmax is a promising noninvasive marker for assessment of small intestinal health. Further studies are warranted to establish its clinical utility for assessing gut status of patients with CD.Am J Gastroenterol advance online publication, 4 June 2013; doi:10.1038/ajg.2013.151.The American Journal of Gastroenterology 06/2013; 108(8). DOI:10.1038/ajg.2013.151 · 9.21 Impact Factor