Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study.
OBJECTIVE
In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy.


METHODS
Forty-one adults suspected of coeliac disease owing to increased density of mucosal gamma(delta)+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls.


RESULTS
Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects.


CONCLUSIONS
Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.
Kaukinen
Katri
K
Department of Tissue Typing, Finnish Red Cross Blood Service, Helsinki, Finland.
Peräaho
Markku
M
Collin
Pekka
P
Partanen
Jukka
J
Woolley
Nina
N
Kaartinen
Tanja
T
Nuutinen
Tuula
T
Halttunen
Tuula
T
Mäki
Markku
M
Korponay-Szabo
Ilma
I
D000328:Adult; D002446:Celiac Disease / Q000175:diagnosis* / Q000178:diet therapy / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005983:Glutens / Q000008:administration & dosage*; D006683:HLA-DQ Antigens / Q000032:analysis; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D007421:Intestine, Small / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism*
D006683:HLA-DQ Antigens; D007070:Immunoglobulin A; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins