Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study

Scand J Gastroenterol. 2005 May;40(5):564-72. doi: 10.1080/00365520510023422.

Abstract

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.

Material and 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Celiac Disease / diagnosis*
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Female
  • GTP-Binding Proteins / immunology
  • GTP-Binding Proteins / metabolism*
  • Glutens / administration & dosage*
  • HLA-DQ Antigens / analysis
  • Humans
  • Immunoglobulin A / analysis*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / pathology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology
  • Transglutaminases / metabolism*

Substances

  • HLA-DQ Antigens
  • Immunoglobulin A
  • Glutens
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins