Expression of immune sensitization to epithelial cell-associated components in the cotton-top tamarin: a model of chronic ulcerative colitis.
Chronic colitis is present in up to 50% of adult cotton-top tamarins, but the etiology is unknown. To explore one putative immunopathogenic pathway for the chronic colitis, we determined whether immune sensitization to macromolecules associated with mucosal epithelium of intestine (designated ECAC) had occurred in this primate species. Specifically, we sought to define (a) whether antigenic determinants associated with ECAC are present on tamarin gut epithelium in vivo; (b) if immunoglobulin, capable of binding ECAC, is detectable in tamarin serum; (c) whether the presence of ECAC-specific immunoglobulin is positively correlated with age of the animal or the severity of the colitis, or both; and (d) the number of glycoprotein fractions composing ECAC (denoted as P1 through P4) that are reactive with tamarin immunoglobulin. Expression of ECAC was found by immunofluorescence using characterized oligo-specific or monoclonal antibody: tamarin intestinal epithelium--but not lamina propria, muscularis mucosae, subserosa, or glycocalyx--demonstrated determinants of the ECAC antigen system. Furthermore, coded sera from 10 tamarins with biopsy-proven inflammation involving colonic intestinal mucosa and in which disease activity was moderate to severe showed ECAC-specific cytotoxicity of 3.6% +/- 1.6%. Test values for 9 of 10 of those animals were above the upper limit of normal for the assay (2.1%), and exceeded the level of lysis found with serum from histologically normal tamarins less than 2 yr old (less than 0.3%). When the data were reanalyzed by age of the animal, the incidence of ECAC-specific cytotoxicity correlated with age greater than 2 yr (r = 0.86, p less than 0.001). Epithelial cell-associated component-specific serum binding was confirmed by a second methodology (enzyme-linked immunosorbent assay), where the A405 for tamarins with lesions of moderate-severe grade (0.35 +/- 0.26) clearly exceeded that for young tamarins who were histologically normal (0.02 +/- 0.039) (p less than 0.05). Most of the reactivity was directed toward the P1 fraction of ECAC. Thus, immune sensitization to a fraction of macromolecules associated with colonic epithelium has been found in the cotton-top tamarin, analogous to findings in humans with chronic inflammatory bowel disease.
Winter
H S
HS
Combined Program in Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Crum
P M
PM
King
N W
NW
Sehgal
P K
PK
Roche
J K
JK
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002143:Callitrichinae / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000276:immunology; D003106:Colon / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male
D001324:Autoantigens; D000939:Epitopes