New Serology Assays Can Detect Gluten Sensitivity among Enteropathy Patients Seronegative for Anti–Tissue Transglutaminase

Abstract

Some patients with celiac disease (CD) may be seronegative with the commonly used test for IgA anti-tissue transglutaminase (anti-tTG) antibodies. Our aim was to explore whether newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs) or other TG isoenzymes as antigen are useful for detecting gluten sensitivity in IgA anti-tTG-seronegative patients. We assayed serum samples obtained at diagnosis from (a) anti-tTG-seronegative patients with a CD-like enteropathy (n = 12), (b) skin biopsy-proven dermatitis herpetiformis (DH) patients (n = 26), and (c) IgA anti-tTG-positive CD patients (n = 26). All patients had typical total IgA concentrations. All patients underwent intestinal biopsy and serum testing for (a) detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics), (b) simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics), and (c) detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). All anti-tTG-seropositive patients also tested positive in anti-DGP assays. Overall, tTG/DGP Screen detected 6 (31.6%) of the 19 anti-tTG seronegatives, and anti-DGP Dual produced positive results in 5 (26.3%) of these cases. Whereas both assays detected 2 anti-tTG-negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 identified 7 (36.8%) of the 19 anti-tTG-negative patients, 5 of which were also positive for anti-DGP. Detection of anti-DGP with tTG/DGP Screen or anti-DGP Dual, or detection of antibodies to other TG isoenzymes, enhances the sensitivity for detecting gluten sensitivity among non-IgA- deficient, anti-tTG-seronegative patients with CD-like enteropathy.