Microbial Transglutaminase-The Food Additive, a Potential Inducing Factor in Primary Biliary Cholangitis

Microbial transglutaminase (mTG) is a bacterial survival factor, which is frequently used as a food additive. This results in the formation of immunogenic epitopes that may cause autoimmunity. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease characterized by the presence of characteristic autoantibodies. The aim of this work was to determine epitope similarity and cross-reactivity between mTG- and PBC-specific antigens and to investigate whether the microbial enzyme may be associated with the induction of autoimmunity due to epitope similarity and cross-reactivity. Monoclonal and polyclonal antibodies against mTG were applied to nine different PBC-specific antigens using ELISA technique. They reacted significantly with four out of nine antigens. This reaction was most pronounced for gp210 and PML protein. We also performed in vitro studies on the impact of the mTG on the specific antigen-antibody binding using sera of PBC patients. We found four PBC-specific antigens that share homology with mTG sequences. We noticed inhibition of this specific binding by the mTG to the PDC M2, gp210, PML, and KLHL12 protein. Microbial mimics may be the major targets of cross-reactivity with human-specific antigens. Cross-reactivity may indicate a link between mTG and the development of autoimmune diseases.