title: Evidence of a selective epitope loss of anti-transglutaminase immunoreactivity in gluten-free diet celiac sera: a new tool to distinguish disease-specific immunoreactivities.
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.
authors.affiliation: Dept. of Clinical Sciences, University of Rome La Sapienza, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. claudio.tiberti@uniroma1.it
authors.forename: C
authors.initials: C
authors.lastname: Tiberti
authors.forename: M
authors.initials: M
authors.lastname: Bonamico
authors.forename: F
authors.initials: F
authors.lastname: Dotta
authors.forename: A
authors.initials: A
authors.lastname: Verrienti
authors.forename: M
authors.initials: M
authors.lastname: Di Tola
authors.forename: E
authors.initials: E
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Ferri
authors.forename: R
authors.initials: R
authors.lastname: Nenna
authors.forename: A
authors.initials: A
authors.lastname: Picarelli
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000293:Adolescent; D000328:Adult; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D002446:Celiac Disease / Q000097:blood / Q000178:diet therapy / Q000201:enzymology* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D005260:Female; D005983:Glutens / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011503:Transglutaminases / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D005983:Glutens; D011503:Transglutaminases