Gluten sensitivity in the rectal mucosa of first-degree relatives of celiac disease patients.
OBJECTIVE
Rectal gluten challenge is a simple, sensitive, and specific test of mucosal gluten sensitivity. Our aims in this study were to evaluate gluten sensitivity in a group of relatives of celiac patients and to compare these findings with those obtained on small bowel histology, celiac disease-related serology, and HLA typing.


METHODS
A 4-h rectal gluten challenge was performed with 6 g of crude gluten in saline solution in 29 first-degree relatives, 20 well-diagnosed celiac patients, and 10 subjects in whom celiac disease had been excluded. The number of intraepithelial lymphocytes in pre- and postchallenge frozen rectal biopsies (pan T-cell immunocytochemistry) was quantified by computerized image analysis.


RESULTS
The intraepithelial lymphocyte response after gluten instillation was significantly higher in celiac disease patients (median, 126% increase above the baseline count; 95% confidence interval: 61-213%) compared with control subjects (median, -5%; 95% confidence interval: -29-5%). Using a cut-off of 20% change in intraepithelial lymphocyte count, 14 relatives (48%) showed a celiac-like response. Two of these subjects had partial villous atrophy and increased lymphocyte counts in the small bowel mucosa. One of them also exhibited a positive celiac disease-related serology and the typical celiac human lymphocyte antibody (HLA) DQ2. The remaining 12, and all those relatives with a negative challenge, had normal small bowel mucosa and were negative for antigliadin and endomysial antibodies. The characteristic celiac HLA (DQA1 0501 DQB1 0201 heterodimer) was identified in five relatives with positive challenge (including the patient with more severe mucosal atrophy) but was also present in eight relatives with no evidence of gluten sensitivity in the rectal mucosa.


CONCLUSIONS
Our study characterizes a subgroup of relatives of celiac patients who show mucosal evidence of sensitization after local instillation of gluten in the rectum but who have no other features of celiac disease.
Dezi
R
R
Clinical Department, Gastroenterology Hospital Dr. Carlos Bonorino Udaondo, Universidad del Salvador, Buenos Aires, Argentina.
Niveloni
S
S
Sugai
E
E
Pedreira
S
S
Smecuol
E
E
Vazquez
H
H
Doldan
I
I
Cabanne
A
A
Boerr
L
L
Valero
J
J
Kogan
Z
Z
Mauriño
E
E
Bai
J C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004386:Duodenum / Q000473:pathology; D005260:Female; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D006680:HLA Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005983:Glutens; D005903:Gliadin