Changes in the pattern of expression of Fatty Acid Binding Proteins in small intestine in untreated Coeliac Disease

GARCIA, MARINA; BOTASSO, NATALIA; BONDAR, CONSTANZA; CORSICO, BETINA; CHIRDO, FERNANDO

Congreso; 9th Meeting of the European Mucosal Immunology Group; 2014

Coeliac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Fully differentiated epithelial cells express two isoformsof fatty acid binding proteins (FABPs): intestinal and liver, I- andLFABP, respectively. I- and LFABPs belong to a family of small cytosolic proteins which bind and transport long chain fatty acids, butalso have other important biological roles in signalling pathways,particularly those related to PPARs which link lipid metabolism andinflammatory process.The aim of this work was to analyse the pattern of expression ofI- and LFABP in small intestine in normal tissues and in those fromuntreated CD patients as well as the evaluation of IFABP serum levels in CD patients and non-CD controls. Expression of I- andLFABP in duodenal tissues was assessed by confocal fluorescencemicroscopy using specific polyclonal antibodies and by quantitativePCR. Immunofluorescence analysis showed a differential pattern ofexpression for both FABPs when normal tissue and severe enteropathy were compared. I- and LFABP were expressed in the epitheliumin healthy mucosa and in the remaining epithelium in partial ortotal villus atrophy. Slight labelling for IFABP was also observed inthe crypts in healthy mucosa. Remarkably, FABPs expression wasclearly increased in the crypts of intestinal mucosa in untreated CD.Quantitative PCR analysis showed that mRNA levels for LFABP werehigher than those for IFABP in normal tissue. Employing bactin ashousekeeping gene, I- and LFABP mRNA levels were lower in duodenal samples from adult untreated CD patients than in healthy controls (P < 0.01). In paediatric population this difference was notobserved. On the other hand, when villin was used as reference, thelevels of both FABPs were increased in enteropathy. Using a commercial quantitative ELISA, we observed that IFABP serum levelswere higher in adult untreated CD patients compared with healthycontrols (P < 0.0001), patients on Gluten free diet (P = 0.023) andinflammatory bowel disease patients (P < 0.001).In conclusion, IFABP, which is likely released from the damagedenterocyte, can be used as a biomarker providing additional information in diagnosis and follow up of CD. The marked increase in Iand LFABP expression in the crypts may reflect an accelerated rateof enterocyte differentiation as compensatory mechanism due to theincrease in epithelial loss