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

Abstract

Abstract Background: 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. Methods: 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). Results: 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. Conclusions: 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.