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.
February 2003
Gut;Feb2003, Vol. 52 Issue 2, p199
Academic Journal
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 established. Aims: To evaluate whether antigens other than TG2 contribute to EMA/ARA/JEA reactions. Patients: Serum samples from 61 EMA/ARA/JEA positive untreated patients with coeliac disease, 40 dermatitis herpetiformis patients, and 34 EMA/ARA/JEA negative non-coeliac controls were tested. Methods: TG2 knockout (TG2-/-) and wild-type mouse oesophagus, jejunum, liver, and kidney sections, and TG2-/- sections coated with human recombinant TG2 were used as substrates in single and double immunofluorescent studies for patient IgA binding and tissue Iocalisation of TG2, fibronectin, actin, and calreticulin. Results: None of the patient serum samples elicited EMA, ARA, or JEA binding in TG2-/morphologically normal tissues. In contrast, 96 of 101 gluten sensitive patient samples (95%) reacted with wild-type mouse tissues and all 101 reacted in EMA/ARA/JEA patterns with TG2-/- mouse tissues coated with human TG2. Serum IgA binding to TG2-/- smooth muscle cells was observed in Iow titres in 31.1%, 27.5%, and 20.5%, and to TG2-/- epithelium in 26.3%, 5.0%, and 8.8% of coeliac, dermatitis herpetiformis, and control samples, respectively. These positivities partly colocalised with actin and calreticulin but not with TG2 or fibronectin. Conclusions: EMA/ARA/JEA antibody binding patterns are exclusively TG2 dependent both in coeliac and dermatitis herpetiformis patients. Actin antibodies are responsible for some positivities which are not part of the EMA/ARA/JEA reactions.


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