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 post-translational 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 signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, 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 related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 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 coeliac 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.

• Authors: Sarolta Kárpáti, Miklós Sárdy, Krisztián Németh, Balázs Mayer, Neil Smyth, Mats Paulsson, Heiko Traupe
• Journal: Experimental dermatology (Exp Dermatol) Vol. 27 Issue 8 Pg. 807-814 (08 2018) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 28940785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Autoantibodies
• Epitopes
• transglutaminase 5
• Transglutaminases

Topics

• Animals
• Apoptosis
• Autoantibodies (immunology)
• Celiac Disease (immunology)
• Cell Lineage
• Dermatitis Herpetiformis (enzymology, immunology)
• Disease Models, Animal
• Epitopes (immunology)
• Humans
• Mice
• Mice, Transgenic
• Mutation
• Phenotype
• Signal Transduction
• Skin (enzymology, immunology)
• Transglutaminases (genetics, physiology)