doi:10.1016/j.clim.2006.05.009
Copyright © 2006 Published by Elsevier Inc.
Evidence of a selective epitope loss of anti-transglutaminase immunoreactivity in gluten-free diet celiac sera: A new tool to distinguish disease-specific immunoreactivities
C. Tibertia,
,
, M. Bonamicob, F. Dottac, A. Verrientia, M. Di Tolaa, E. Liud, M. Ferrib, R. Nennab, A. Picarellia and G.S. Eisenbarthd
aDept. of Clinical Sciences, University of Rome “La Sapienza”, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy
bPediatrics, University “La Sapienza”, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy
cDepts. of Internal Medicine and of Endocrine and Metabolic Sciences, University of Siena, Italy
dBarbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences, Center, CO 80309-0482, USA
Received 3 March 2006;
accepted 16 May 2006.
Available online 23 June 2006.
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Abstract
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.
Keywords: Celiac disease; Human tissue transglutaminase; Epitopes; Autoimmunity
Fig. 1. Reactivity against full-length tTG (1–687), tTG (227–687) and tTG (473–687) constructs in 64 classic celiac disease patients (CD). The y axis indicates autoantibody indexes relative to each CD patient. The x axis indicate the different times of gluten-free diet analyzed in the study (disease diagnosis, a mean time of 6 months and 2 years of gluten-free diet, respectively). The y axis shows the autoantibody titers expressed as an index. The horizontal dashed lines represent the limit of positivity of the RIA method, defined by 99th percentile of 112 normal sera. Bars indicate median value.
Fig. 2. Examples of tTG (1–687) (squares), tTG (227–687) (circles) and tTG (473–687 (triangles) autoantibody individual patterns of reactivity in 4 celiac patient sera at disease diagnosis and after gluten-free diet (GFD). Full and empty symbols indicate autoantibody positivity and negativity, respectively. The x axis indicates the different times of GFD. The y axis shows the autoantibody titers expressed as an index.
Table 1.
tTG construct immunoreactivities in 64 classic celiac patients

a vs. c P = 0.003; g vs. i P < 0.0001; k vs. n P = 0.001; s vs. t P = 0.001; d vs. f P = 0.046; h vs. j P < 0.0001; m vs. p P < 0.0001; t vs. u P = 0.019; b vs. d P < 0.0001; n vs. q P = 0.03; c vs. e P < 0.0001; p vs. r P = 0.004