Coeliac disease research and clinical practice: maintaining momentum into the twenty-first century.

Recent research shows that each word in the definition of coeliac disease, permanent gluten sensitive enteropathy, must now be reviewed, revised or reinterpreted. Permanent--but there are now well-documented cases of acquired disease, and perhaps also partial recovery of gut gluten tolerance. Enteropathy--gluten sensitivity is expressed in a spectrum, with a mild form seen as normal architecture with high count of intraepithelial lymphocytes. Gluten--the provoking agent--Investigators are intensively working to identify the precise toxic sequence, and to establish how this will link in with new genetic information. Mechanism of sensitivity? or hypersensitivity?--Critical to this is new knowledge on the modulation and regulation of immunity to intestinal antigens, including gliadin. A hypothesis is presented, as to the pathogenesis of gluten-sensitive enteropathy, which combines concepts of oral tolerance and of the regulation of expression of delayed type hypersensitivity reactions in the gut mucosa.