Relationship between intestinal permeability to [51Cr]EDTA and inflammatory activity in asymptomatic patients with Crohn's disease

Abstract

The relationship between intestinal permeability to an oral dose (100 mu Ci) of [51CR]EDTA and the inflammatory activity of Crohn's disease was studied in 63 adult patients (32 unresected and 31 resected) who underwent 162 evaluations. The results of the [51CR]EDTA test were compared with the serum levels of the acute-phase reactant proteins (APRP) and with the result of the [111In]leukocyte scanning, respectively, as an indirect and direct method to assess intestinal inflammation. In a group of healthy adult controls, the upper normal value for the 24-hr urinary [51CR]EDTA excretion was 3.61 (97.5% percentile) and the mean coefficient of variation was 21%. Sensitivity and specificity of the [51CR]EDTA test in identifying active inflammation expressed by increased serum levels of APRP were, respectively, 97% and 54% in the unresected group and 68% and 52% in the resected group of patients. The low specificity of the test was due to the presence of increased [51CR]EDTA urinary excretion in about half the cases with normal serum levels of APRP. The [111In]leukocyte scanning was performed in a subgroup of 11 patients (three unresected and eight resected) with normal serum levels of APRP, six with increased and five with normal [51CR]EDTA urinary excretion. All six patients with increased intestinal permeability had a positive 111In image of mild to moderate degree of activity. A positive 111In scan was present in two of the five patients with normal permeability; these were two resected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Inflammatory bowel disease is associated with changes of enterocytic junctions

“…Despite other reports (2,17,26,33,39,44,45,52) that intestinal permeability is clearly increased in noninflamed IBD mucosa, especially in CD patients and their relatives, our data collectively do not indicate a primary defect in the expression of major junctional proteins in IBD. However, further as yet undefined junctional components or incompletely characterized molecules such as junction adhesion molecules (28) might be involved in the regulation of intestinal permeability.…”

“…Jankowski and co-workers (19) have shown a strong correlation between the deregulation of two classic cadherin molecules, E-and P-cadherin, and the progression of human colitis (20). Furthermore, changes of intestinal permeability have been reported in patients with IBD (39,52). In UC, perturbations in permeability seem to be limited to the inflamed intestinal segment, whereas in CD, discrete intestinal permeability alterations have been observed not only in gut tissues with evident intestinal lesions but also in areas lacking any sign of macroscopic injury (10,27,38).…”

Loss of the Tight Junction Protein ZO-1 in Dextran Sulfate Sodium Induced Colitis

“…Several studies have shown that the appearance of the inflammatory infiltrate in the mucosa is not the initial event [8,12]. The first histological evidence of DSS injury is a disappearance of the basal crypt with separation of the crypts from the muscularis mucosa.…”

Intestinal permeability, leaky gut, and intestinal disorders

“…Intestinal permeability may be the best current approach toward an objective, measurable, easy-to-perform, and reproducible method for assessing the degree of activity of Crohn's disease. Results from several studies indicate that the permeability rate in patients with active Crohn's disease reflects the severity and activity of the disease beyond its elevated baseline level [24][25][26]. More recently, studies have shown that shorter urinary collections can be used to achieve the same degree of accuracy of permeability assessment as with the 6-hour urine collection [27].…”