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Autoimmunity - an Introduction

Gliadin and Celiac Disease

Deamidation of gliadin in immune pathogenesis of celiac disease

The enzyme tissue transglutaminase (tTG) catalyzes the deamidation of the amino acid glutamine and the transfer of protein-bound glutamine residues to primary amines. If the reaction involves the ε-amino function of a lysine residue as well as the γ-glutamyl group of the glutamine, the result can be intra- or intermolecular cross-linking. The complex made from tTG and bound gliadin seems to have an immunogenic effect and stimulates the formation of antibodies against tTG. Further reaction and hydrolysis converts one glutamine residue of the gliadin into glutamic acid. This changes the charge and three-dimensional structure of the gliadin, which can now activate the immune system.

Fig.1
Deamidation of gliadin peptides by tissue transglutaminase
© Orgentec Diagnostika

This immune reaction has a genetic component: individuals who carry the HLA-DQ2 or HLA-DQ8 alleles are particularly susceptible. Unlike native gliadin, the gliadin peptides modified by tTG can form stable hydrogen bonds by way of the glutamic acid residue, binding to the HLA-DQ2 or HLA-DQ8 molecules on the surface of antigen-presenting cells.

Fig.2
A gliadin peptide bound to HLA-DQ2
© Orgentec Diagnostika

3D model of the gliadin peptide bound to HLA-DQ2

These stimulate T cells to produce cytokines, starting a cascade of reactions that eventually lead to the destruction of the intestinal lining.

Diseases with an autoimmune background are more common than usually thought. Sometimes they can be distinguished by characteristic symptoms like elevated levels of glucose in the blood of patients suffering from diabetes. But frequently they show symptoms similar to other inflammatory diseases, making a correct diagnosis difficult.

In autoimmune diseases, the immune system considers the body’s own structures to be "foreign" and attempts to eliminate them by using specific autoantibodies to proteins like tTG in celiac disease, to proteinase 3 in Wegener's granulomatosis or antibodies to mutated citrullinated vimentin (MCV) in cases of rheumatoid arthritis. Sometimes these autoantibodies may occur even years before onset of the disease.

Laboratory tests that detect autoantibodies in the blood sera of affected patients are a valuable tool for the diagnosis of various autoimmune diseases. They support the attending physician in finding the right diagnosis and in monitoring therapy outcome.

Reference autoimmunity

Murphy, K. M.; Travers, P.; Walport, M. (2007): Janeway's Immunobiology. Garland Science ,

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