Cellular hypersensitivity to a synthetic dodecapeptide derived from human adenovirus 12 which resembles a sequence of A-gliadin in patients with coeliac disease.
The human intestinal adenovirus serotype 12 (Ad12) may be implicated in the pathogenesis of coeliac disease by virtue of immunological cross reactivity between epitopes shared by its early region E1b protein and A-gliadin. In the present study a synthetic dodecapeptide from the corresponding viral epitope (Ad12E1b, residues 384-395) was tested for its effect on peripheral blood mononuclear cells from 22 treated and eight untreated patients with coeliac disease, 22 healthy subjects, 11 patients with ulcerative colitis, and 11 patients with Crohn's disease by an indirect leucocyte migration inhibition assay. In addition, the effect of both the viral and the gliadin synthetic peptides was studied by proliferation and migration assays simultaneously performed in an unselected subgroup of 12 treated coeliac patients and 12 healthy subjects of the study. Coeliac patients with untreated disease showed no response to the viral peptide compared with treated patients (p greater than 0.1). Treated coeliac patients showed a significantly different response from healthy control subjects and control patients with disease (p less than 0.001) which was dependent on the concentration of the viral peptide. In the subgroup of the treated coeliac patients (n = 12) there was a significant correlation between the responses in the migration and the proliferation assay using either the viral (p less than 0.02) or the gliadin (p less than 0.005) peptide at the highest concentration (33.3 micrograms/ml). Furthermore, the responses obtained using viral peptide correlated significantly with the responses obtained with gliadin peptide in both the migration (p less than 0.001) and the proliferation (p less than 0.001) assays. These results show that in coeliac patients there is pronounced cross reactivity at the level of T cell recognition between synthetic peptides derived from the Ad12 and A-gliadin. This antigenic cross reactivity may be involved in the pathogenesis of coeliac disease.
Gastroenterology Unit, Radcliffe Infirmary, Oxford.
G J
GJ
Mantzaris
J A
JA
Karagiannis
J D
JD
Priddle
D P
DP
Jewell
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000276:immunology*; D000328:Adult; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D002464:Cell Migration Inhibition; D000939:Epitopes / Q000276:immunology; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D010940:Plant Proteins / Q000276:immunology*
D017456:Adenovirus Early Proteins; D000957:Antigens, Viral, Tumor; D000939:Epitopes; D009842:Oligopeptides; D009856:Oncogene Proteins, Viral; D010940:Plant Proteins; D005903:Gliadin