Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review.
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.
Pediatric Research Center, University of Tampere and Tampere University Hospital, Finn Medi 3, 33520, Tampere, Finland.
Tiina
T
Rauhavirta
Pediatric Research Center, University of Tampere and Tampere University Hospital, Finn Medi 3, 33520, Tampere, Finland.
Minna
M
Hietikko
School of Medicine, University of Tampere, Tampere, Finland.|Department of Dermatology, Tampere University Hospital, Tampere, Finland.
Teea
T
Salmi
Pediatric Research Center, University of Tampere and Tampere University Hospital, Finn Medi 3, 33520, Tampere, Finland. katri.lindfors@uta.fi.
Katri
K
Lindfors
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases; D001402:B-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D002648:Child; D055050:Diet, Gluten-Free; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D005903:Gliadin / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D015995:Prevalence; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012307:Risk Factors; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
Celiac disease; Transglutaminase 2; Transglutaminase 2 autoantibodies