Gastroenterol Hepatol. 2010 Feb 1. [Epub ahead of print]

[Immunology of celiac disease.]
[Article in Spanish]

Arranz E, Garrote JA.

Laboratorio de Inmunología de las Mucosas, Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, Valladolid, España.

Celiac disease is an inflammatory disorder of the small intestine induced by intake of wheat gluten and other prolamines in genetically susceptible individuals. This disease is manifested by an increased number of intraepithelial and lamina propria lymphocytes, villous atrophy, tissue remodeling and the presence of anti-transglutaminase antibodies. The most widely accepted pathogenic model is based on adaptive immunity after T CD4(+)lymphocyte stimulation by tissue transglutamine-modified gluten peptides and HLA-DQ2/DQ8 restriction, which produce proinflammatory cytokines. Gluten also activates innate immunity and epithelial cytotoxicity mediated by intraepithelial lymphocytes. Although the effect of specific antibodies remains unclear, the availability of serological and immunogenetic markers as diagnostic tools has increased our knowledge of celiac disease and has led to a reevaluation of the diagnostic criteria, especially in adults with minimal or atypical disease expression. Copyright © 2009 Elsevier España, S.L. All rights reserved.

PMID: 20129704 [PubMed - as supplied by publisher]

Summation:

The intraepithelial lymphocytes found in the gastrointestinal tract are primarily gamma-delta T-cell receptors that express CD8, which binds to MHC class I molecules. However, the pathogenesis of celiac disease leads to the accumulation of CD4 T cells in the intraepithelial and lamina propria of the mucosal lining of the gastrointestinal tract.

Nearly all celiacs express the HLA-DQ2 class II MHC allele. The HLA-DQ2 molecule has an unusual binding cleft structure. Only peptides with certain negative residues bind strongly to HLA-DQ2 to form peptide:HLA-DQ2 complex.

The protein alpha-gliadin is a major component of gluten. Alpha-gliadin is deaminated by the enzyme transglutaminase which, converts glutamine residues to negatively charged glutamic acid. The modified alpha-gliadin peptide can then bind to HLA-DQ2 and MHC class II. The bound peptide then activates CD4 T cells specific to gluten and produces interferon which causes inflammation.

IgA and IgG autoantibodies to transglutaminase are markers of celiac disease although celiac is not considered to be an autoimmune disease.