title: Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.
abstract: The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.
authors.affiliation: Department of Medicine, University of Manchester School of Medicine, United Kingdom.
authors.forename: D E
authors.initials: DE
authors.lastname: Loft
authors.forename: M N
authors.initials: MN
authors.lastname: Marsh
authors.forename: G I
authors.initials: GI
authors.lastname: Sandle
authors.forename: P T
authors.initials: PT
authors.lastname: Crowe
authors.forename: V
authors.initials: V
authors.lastname: Garner
authors.forename: D
authors.initials: D
authors.lastname: Gordon
authors.forename: R
authors.initials: R
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D002199:Capillary Permeability / Q000187:drug effects; D002446:Celiac Disease / Q000473:pathology*; D005260:Female; D005983:Glutens / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D012007:Rectum / Q000187:drug effects
chemical_list: D005983:Glutens