Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review

Abstract

Celiac disease is a common inflammatory disorder with a prevalence of 1-2 % in which a distinct dietary wheat, rye, and barley component, gluten, induces small-bowel mucosal villous atrophy, crypt hyperplasia, and inflammation. The small-bowel mucosal damage can be reversed by a strict lifelong gluten-free diet, which is currently the only effective treatment for the condition. A key player in the pathogenetic process leading to the enteropathy is played by a protein called transglutaminase 2 (TG2), which is able to enzymatically modify gluten-derived gliadin peptides. The TG2-catalyzed deamidation of the gliadin peptides results in their increased binding affinity to the disease-predisposing human leukocyte antigen (HLA) DQ2 and DQ8 molecules, thus enabling a strong immune response to be launched. Blocking the enzymatic activity of TG2 has thus been suggested as a suitable novel pharmacological approach to treat celiac disease. By virtue of its transamidation capacity, TG2 is also able to cross-link gliadin peptides to itself, this resulting in the generation of TG2-gliadin peptide complexes whose presence might provide an explanation for the generation of the TG2 autoantibodies characteristic of celiac disease. Due to their excellent specificity for the disorder, the TG2-targeted autoantibodies are widely used in the diagnostics as a first-line test to select patients for gastrointestinal endoscopy. More recently, it has come to be appreciated that these autoantibodies and also the TG2-specific B cells might play an active role in the disease pathogenesis. In this review, we assess the role of TG2, TG2-specific B cells, and autoantibodies in celiac disease.

Characterisation of a novel cold‐adapted calcium‐activated transglutaminase: implications for medicine and food processing

“…The coeliac disease is a gluten‐induced immune‐mediated disease characterised by a specific genetic genotype (HLA‐DQ2 and HLA‐DQ8 genes) and autoantibodies (anti‐tissue transglutaminase) . A key player is transglutaminase 2, which is able to modify gluten‐derived gliadin peptide . The deamination of the gliadin peptide results in increased binding affinity to the human leucocyte antigen (HLA) DQ2 and DQ8 molecules, triggering a strong immune response .…”

“…A key player is transglutaminase 2, which is able to modify gluten‐derived gliadin peptide . The deamination of the gliadin peptide results in increased binding affinity to the human leucocyte antigen (HLA) DQ2 and DQ8 molecules, triggering a strong immune response . In plants, TGs have been linked to the development of chloroplasts , while TGs in fish seem to be involved in immune defence .…”

Elevated transglutaminase‐2 expression in the epidermis of psoriatic skin and its role in the skin lesion development

“…1 Although psoriasis has served as a model for in-depth investigations of several adhesion molecule interactions that are of general importance in the generation of inflammatory reactions, the specific pathogenic mechanism of psoriasis has not been fully illustrated. The prevalence of psoriasis is relatively high in the general population, ranging 0.6-4.8%.…”

“…Psoriasis has been classified into five subtypes, comprising plaque psoriasis (psoriasis vulgaris), guttate (droplet), inverse psoriasis (intertriginous or flexural psoriasis), pustular psoriasis and erythrodermic psoriasis, and 90% of cases of psoriasis were found to be plaque psoriasis. 1 Although psoriasis has served as a model for in-depth investigations of several adhesion molecule interactions that are of general importance in the generation of inflammatory reactions, the specific pathogenic mechanism of psoriasis has not been fully illustrated. Early diagnosis and comprehensive management of patients with psoriasis is a very important issue.…”

“…That transglutaminase (TG)2 plays a vital role in celiac disease is well documented, 1 and it has been also found to be associated with many human diseases, such as cancer progression, immunoglobulin A nephropathy, multiple sclerosis, lung fibrosis, chronic obstructive pulmonary disease, 2 and neurodegenerative diseases, for example, Alzheimer's disease, 3 Huntington's disease, 4 and Parkinson's disease. 5 In addition, TG-deficiency syndromes have been identified in the skin, including Netherton syndrome (autosomal recessive congenital ichthyosis featuring chronic inflammation of the skin), 6 lamellar ichthyosis (severe congenital skin disorder characterized by generalized large scales and variable redness) 7 and Darier-White disease (a chronic and unremitting burden), 8 and these diseases were involved with aberrant keratinocyte differentiation, parakeratosis and acantholysis.…”