Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease.
BACKGROUND
Diagnosis of many immune-mediated diseases is helped by detection of antibodies directed against the pathogenetic (self or foreign) antigen. In coeliac disease (CD), we have a situation in which antiendomysial antibodies (EMA), which are not specific for the pathogenetic antigen, reach a specificity and sensitivity of detection of CD approaching 100%, whereas detection of antibodies against gliadin (AGA), the pathogenetic antigen, is far less specific and sensitive in diagnosis. No direct evidence of a relation between gluten/gliadin challenge and EMA production exists. We tried to establish whether the small intestine of CD patients is the site of EMA production and whether gliadin challenge could induce their release.


METHODS
Small intestine biopsy samples from treated (23) and untreated (16) CD patients and controls (18) were cultured in vitro for 24-48 h in the presence of gliadin, another alimentary antigen, or medium. EMA and AGA were detected in the supernatants of these organ culture biopsy samples by ELISA and immunofluorescence technique, respectively.


RESULTS
No EMA were found in the culture supernatants of biopsy samples of 18 controls, whereas they were detected in the culture supernatants of all 16 untreated CD patients irrespective of gliadin challenge. Conversely, EMA were not detected in supernatants of biopsy samples cultured in medium only from 23 treated CD patients, but were detected in 17 of the 23 biopsy samples challenged with gliadin.


CONCLUSIONS
Our results suggest that a more complex pathogenetic mechanism than normally accepted is involved in CD. Furthermore, our findings raise the possibility that EMA, or the antigen recognised by them, are involved directly in the pathogenesis of CD.
Picarelli
A
A
Cattedra dl Gastroenterología, University La Sapienza, Rome, Italy.
Maiuri
L
L
Frate
A
A
Greco
M
M
Auricchio
S
S
Londei
M
M
D000917:Antibody Formation / Q000187:drug effects; D000941:Antigens; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D005903:Gliadin / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007421:Intestine, Small / Q000276:immunology; D009132:Muscles / Q000276:immunology*; D012016:Reference Values
D000941:Antigens; D001323:Autoantibodies; D005903:Gliadin