Coeliac autoantibodies can enhance transamidating and inhibit GTPase activity of tissue transglutaminase: dependence on reaction environment and enzyme fitness

J Autoimmun. 2006 Jun;26(4):278-87. doi: 10.1016/j.jaut.2006.03.002. Epub 2006 May 6.

Abstract

Modification of the enzymatic functions of tissue transglutaminase (TG2) by anti-TG2 autoantibodies may play a role in manifestations of coeliac disease. Our aim was to evaluate the effect of coeliac autoantibodies on reactions catalysed by TG2 by a systematic biochemical approach, and in relation to observed clinical presentation type. Coeliac antibodies did not have significant inhibitory effect on transamidation/deamidation activity of TG2 as measured by amine-incorporation into solid and immobilised casein and by ultraviolet kinetic assay. In contrast, immunoglobulins from patients with severe malabsorption enhanced the reaction velocity to 105.4-242.2%. This activating effect was dose-dependent, most pronounced with immobilised glutamine-acceptor substrates, and correlated inversely with the basal specific activity of the enzyme and with dietary treatment. A similar activation could be demonstrated also with the TG2-specific fraction of autoantibodies and in transamidation activity assays which use fibronectin-bound TG2 and thereby mimic in vivo conditions. These results suggest that coeliac antibodies may stabilise the enzyme in a catalytically advantageous conformation. GTPase activity of TG2 decreased to 67.0-73.4% in the presence of antibodies raising the possibility that inhibition of GTPase activity may affect cellular signalling in case coeliac autoantibodies would reach intracellular compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibody Specificity
  • Autoantibodies / immunology*
  • Celiac Disease / enzymology
  • Celiac Disease / immunology*
  • Child
  • Child, Preschool
  • Female
  • GTP Phosphohydrolases / antagonists & inhibitors*
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Infant
  • Male
  • Middle Aged
  • Transglutaminases / antagonists & inhibitors*
  • Transglutaminases / metabolism*

Substances

  • Autoantibodies
  • Immunoglobulin A
  • Immunoglobulin G
  • transglutaminase 2
  • Transglutaminases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins