Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation

Abstract

Transglutaminases (TGs) are structurally and functionally related enzymes that modify the posttranslational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signaling, the function and the fate of cells and extracellular connective tissues. Beside mouse models also human diseases enable us to appreciate the function of various TGs. In this paper skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations relate to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM 3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as celiac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases the epitope spreading is remarkable, while in some inherited pathologies a unique compensation of the lost enzyme function is noted.

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