Evidence of a selective epitope loss of anti-transglutaminase immunoreactivity in gluten-free diet celiac sera: A new tool to distinguish disease-specific immunoreactivities

The aim of the present study was to evaluate the epitope specific humoral human tissue transglutaminase (tTG) immunoreactivity against 3 different human recombinant tTG constructs [(full-length tTG (a.a. 1–687), tTG (a.a. 227–687); tTG (a.a. 473–687)] before and after the introduction of a gluten-free diet (GFD). To this end, sera from 64 celiac disease (CD) subjects on a gluten-containing diet (44 f, 20 m) and after 0.6 ± 0.3 years and 2.1 ± 1.3 years of GFD were studied using a quantitative radioimmunoprecipitation assay. All 64 CD patients at diagnosis were full-length anti-tTG (a.a. 1–687)Ab positive. These Abs significantly decreased in frequency and titer after 6 months and 2 years of GFD. However, at low titers, 64.1% (41/64) of CD patients were still fl-tTG (a.a. 1–687)Ab positive after 2 years of GFD. At disease diagnosis, 70.3% (45/64) of the CD patients had Abs directed against fragments (227–687) and/or (473–687) of the tTG protein. This percentage, after 2 years of GFD, significantly decreased to 18.7%, whereas almost 50% of GFD patients had no tTG (227–687) and tTG (473–687) fragment reactivity, but only persistent, low-titer full-length tTG (1–687)Abs. We suggest that the selective loss of immunoreactivity against tTG (227–687) and tTG (473–687) fragments in CD patients with a GFD, could be due to quantitative decrease of autoreactivity driven by tTG-gliadin interaction underlying celiac disease pathogenesis.