Methods and Composition for Detecting Intestinal Cell-Barrier Dysfunction

A method of detecting intestinal cell barrier dysfunction in a patient comprising

• obtaining an in situ image of a patient's IEC's by probe-based confocal laser endomicroscopy (pCLE), and
• counting IECs in said image to determine the number of gaps in the imaged IECs, where a number of gaps of greater than 2 per hundred cells is indicative of cell barrier dysfunction.

A probe composition for use in detecting intestinal cell barrier dysfunction, comprising

• (a) a first probe comprising a first detectable marker conjugated to a caspase-1 inhibitor, and
• (b) second probe comprising a second detectable marker different from the first marker conjugated to a caspase-3&7 inhibitor.

The probe composition 19, wherein the second probe is a conjugate of Caspase-3/7 Inhibitor I and a fluorochrome different from that of the first-probe fluorochrome.

A method for detecting Crohn's disease in a patient comprising

• (a) staining patient oropharyngeal or buccal epithelial cells with a probe having a detectable marker conjugated to a caspase-1 inhibitor, and
• (b) examining the stained oropharyngeal epithelial cells for the presence of elevated levels of detectable marker, relative to similarly-stained oropharyngeal epithelial cells from a normal individual, as evidence of above-normal levels of caspase-1 associated with the patient oropharyngeal epithelial cells,
• (c) where elevated levels of caspase-1 in the patient oropharyngeal epithelial cells is an indicator of Crohn's disease.