Celiac disease.
Clinically, celiac disease has always been regarded as a wasting, malabsorptive disorder due to disease of the small intestinal mucosa. It has been difficult for clinicians to recognize that this condition is primarily due to sensitization of mesenteric T lymphocytes to wheat protein (gluten) in genetically predisposed (DQ2+) individuals. On contact with dietary-derived gluten in the upper intestine, these sensitized T lymphocytes are activated leading to inflammation of and morphologically altered mucosal architecture: the latter reverts to normal with a gluten-free diet. The circulation of sensitized T lymphocytes to other parts of the intestinal mucosa explains why identical immunopathological inflammation can be induced in ileal and rectal mucosa. It appears, then, that in predisposed DQ2+ subjects, mesenteric T lymphocytes recognize gluten as foreign (non-self) antigen, thereby inducing mucosal pathology secondary to the initiating lymphocyte-protein interaction, analogously to the mucosal lesions that typify graft-vs-host reactions, or nematode or Giaraia infestations. Today, as this article describes, we recognize that celiac disease often exists in a subclinical, or "compensated-latent," form, or with symptoms that do not immediately suggest an origin in the gastrointestinal tract.
Williamson
Debbie
D
Hope Hospital, Medicine, Clinical Sciences Bldg., Salford, Manchester, M68HD, U.K.
Marsh
Michael N
MN
D002446:Celiac Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D004044:Dietary Proteins / Q000009:adverse effects / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000009:adverse effects / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D010940:Plant Proteins / Q000276:immunology*; D055315:Prolamins; D013601:T-Lymphocytes / Q000276:immunology*
D004044:Dietary Proteins; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010940:Plant Proteins; D055315:Prolamins; D005983:Glutens