Autoantibodies of patients with coeliac disease are insufficient to block tissue transglutaminase activity

Dieterich W; Trapp D; Esslinger B; Leidenberger M; Piper J; Hahn E; Schuppan D
November 2003
Gut;Nov2003, Vol. 52 Issue 11, p1562
Academic Journal
BACKGROUND: and aims: Coeliac disease (CD) is characterised by the presence of autoantibodies against tissue transglutaminase (tTG), the endomysial autoantigen. This study was performed to determine the effect of purified autoantibodies on the enzymatic activity of tTG. METHODS: Total IgA and IgG class antibodies and purified anti-tTG autoantibodies were isolated from sera of untreated patients with CD and controls. The inhibitory capacity of the antibodies on tTG activity was checked by a fluorometric assay based on the incorporation of monodansyl cadaverine into casein and by tTG-catalysed cross linking of biotinylated cadaverine to gliadin. RESULTS: The enriched IgA and IgG fractions of five patients with CD and three controls resulted in no significantly different inhibition of enzymatic activity. In contrast, the use of affinity purified anti-tTG autoantibodies of 12 patients with CD led to a dose dependent reduction of tTG activity, compared to control immunoglobulins (n=6). However, the remaining activity was sufficient for cross linking of cadaverine into gliadin, and enzymatic tTG activity was only blocked completely by high concentrations of a monoclonal antibody, which is directed to the active centre of tTG. CONCLUSIONS: Despite a partial inhibitory effect of isolated anti-tTG autoantibodies from patients with CD, residual enzymatic activity remains sufficiently high to cast doubt on their in vivo relevance.


Related Articles

  • A Report on the International Transglutaminase Autoantibody Workshop for Celiac Disease. Li, Marcella; Liping Yu; Tiberti, Claudio; Bonamico, Margherita; Taki, Iman; Dongmei Miao; Murray, Joseph A.; Rewers, Marian J.; Hoffenberg, Edward J.; Agardh, Daniel; Mueller, Patricia; Stern, Martin; Bonifacio, Ezio; Liu, Edwin // American Journal of Gastroenterology;Jan2009, Vol. 104 Issue 1, p154 

    OBJECTIVES: Measurement of transglutaminase autoantibodies (TGAA) is considered to be the most efficient single serologic test for celiac disease (CD) by the American Gastroenterological Association Institute. We hypothesized that a large international collaborative effort toward improving and...

  • Galactosylation of Serum IgA1 O-Glycans in Celiac Disease. Lindfors, Katri; Suzuki, Hitoshi; Novak, Jan; Collin, Pekka; Saavalainen, Päivi; Koskinen, Lotta; Mäki, Markku; Kaukinen, Katri // Journal of Clinical Immunology;Jan2011, Vol. 31 Issue 1, p74 

    In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin...

  • Detection of Autoantibodies Against Tissue Transglutaminase in Patients With Celiac Disease and Dermatitis Herpetiformis. Koop, Irmtraut; Ilchmann, Ralf; Izzi, Leo; Adragna, Amelia; Koop, Herbert; Barthelmes, Hans // American Journal of Gastroenterology;Aug2000, Vol. 95 Issue 8, p2009 

    OBJECTIVE: Endomysial autoantibodies (EmA) are specific for celiac disease. The target antigen has been identified as tissue tranglutaminase (tTG). Our aim was to study the accuracy of a newly developed enzyme-linked immunosorbent assay (ELISA) for easy detection of tTG autoantibodies. METHODS:...

  • High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions. Di Niro, Roberto; Mesin, Luka; Zheng, Nai-Ying; Stamnaes, Jorunn; Morrissey, Michael; Lee, Jane-Hwei; Huang, Min; Iversen, Rasmus; du Pré, M Fleur; Qiao, Shuo-Wang; Lundin, Knut E A; Wilson, Patrick C; Sollid, Ludvig M // Nature Medicine;Mar2012, Vol. 18 Issue 3, p441 

    Celiac disease is an immune-mediated disorder in which mucosal autoantibodies to the enzyme transglutaminase 2 (TG2) are generated in response to the exogenous antigen gluten in individuals who express human leukocyte antigen HLA-DQ2 or HLA-DQ8 (ref. 3). We assessed in a comprehensive and...

  • Majority of Children With Type 1 Diabetes Produce and Deposit Anti-Tissue Transglutaminase Antibodies in the Small Intestine. Maglio, Mariantonia; Florian, Fiorella; Vecchiet, Monica; Auricchio, Renata; Paparo, Francesco; Spadaro, Raffaella; Zanzi, Delia; Rapacciuolo, Luciano; Franzese, Adriana; Sblattero, Daniele; Marzari, Roberto; Troncone, Riccardo // Diabetes;Jul2009, Vol. 58 Issue 7, p1578 

    OBJECTIVE--Anti-tissue transglutaminase (TG2) antibodies are the serological marker of celiac disease. Given the close association between celiac disease and type 1 diabetes, we investigated the production and deposition of anti-TG2 antibodies in the jejunal mucosa of type 1 diabetic children....

  • Missing endomysial and reticulin binding of coeliac antibodies in transglutaminase 2 knockout tissues. Korponay-Szabó, I.R.; Laurila, K.; Szondy, Z.; Halttunen, T.; Szalai, Z.; Dahlbom, I.; Rantala, I.; Kovács, J.B.; Fésüs, L.; Máki, M. // Gut;Feb2003, Vol. 52 Issue 2, p199 

    Background: Autoantibodies against transglutaminase 2 (TG2) are thought to be responsible for the endomysial (EMA), reticulin (ARA), and jejunal antibody (JEA) tissue binding of serum samples from coeliac patients but the exclusive role of TG2 in these staining patterns has not yet been...

  • The role of antitissue transglutaminase assay for the daignosis and monitoring of coeliac disease: a French—Italian muticentre study. Tonutti, E.; Visentini, D.; Bizzara, N.; Caradonna, M.; Cerni, L.; Villalta, D.; Tozzoli, R. // Journal of Clinical Pathology;May2003, Vol. 56 Issue 5, p389 

    Aims: Tissue transglutaminase (tTG) was recently identified as the major autoantigen in coeliac disease. The aim of this multicentre study was to evaluate the impact of a new immunoenzymatic assay for the detection of IgA anti-tGT antibodies. Methods: Seventy four Italian and French clinical...

  • Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ. Esposito, C.; Paparo, F.; Caputo, I.; Rossi, M.; Maglio, M.; Sblattero, D.; Not, T.; Porta, R.; Auricchio, S.; Marzari, R.; Troncone, R. // Gut;Aug2002, Vol. 51 Issue 2, p177 

    Background and aims: Coeliac disease (CD) is a multifactorial disorder which has an autoimmune component characterised by the occurrence of disease specific autoreactive antibodies against the enzyme tissue transglutaminase (tTG). The aim of this study was to investigate whether binding of...

  • Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study. Gomez, Juan C.; Selvaggio, Gisella; Pizarro, Bibiana; Viola, Martin J.; La Motta, Graciela; Smecuol, Edgardo; Castelletto, Roberto; Echeverrıa, Raúl; Vazquez, Horacio; Mazure, Roberto; Crivelli, Adriana; Sugai, Emilia; Mauriño, Eduardo; Bai, Julio C. // American Journal of Gastroenterology;Nov2002, Vol. 97 Issue 11, p2785 

    OBJECTIVE:Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the...


Read the Article


Sign out of this library

Other Topics