In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies

Korponay-Szabó, I. R.; Halttunen, I.; Szalai, Z.; Laurila, K.; Király, R.; Kovács, J. B.; Fésüs, L.; Möki, M.
May 2004
Gut;May2004, Vol. 53 Issue 5, p641
Academic Journal
Background: IgA class serum autoantibodies against type 2 (tissue) transglutaminase (TG2) bind to both intestinal and extraintestinal normal tissue sections in vitro, eliciting endomysial, reticulin, and jelunal antibody reactions. It is not known whether similar binding also occurs in coeliac patients in vivo, and may thereby contribute to disease manifestations. Aims: To investigate intestinal and extraintestinal coeliac tissues for the presence of in vivo bound TG2 specific IgA and its relation to small intestinal mucosal atrophy. Patients: We investi9ated lelunal samples with normal villous morphology from 10 patients with developing coeliac disease who subsequently progressed to a flat lesion, from 11 patients with dermatitis herpetiformis, and from 12 non-coeliac controls. Six extrajelunal biopsy samples (liver, lymph node, muscle, appendix), obtained based on independent clinical indications from patients with active coeliac disease, were also studied. Methods: Double colour immunofluorescent studies For in situ IgA, TG2, and laminin were performed. IgA was eluted from tissue sections and tested for TG2 specificity by enzyme linked immunosorbent assay and indirect immunofluorescence. Results: IgA (in one IgA deficient case IgG) deposition on extracellularly located TG2 was detected in lelunal and extra jelunal specimens of all coeliac patients, and also in seven of 11 dermatitis herpetiformis patients, of whom two had no circulating endomysial antibodies. IgA eluted from extraintestinal coeliac tissues was targeted against TG2. Conclusions: Coeliac IgA targets jejunal TG2 early in disease development even when endomysial antibodies are not present in the circulation. Extraintestinal target sites of coeliac lgA further indicate that humoral immunity may have a pathogenetic role.


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