Tissue transglutaminase antibodies in individuals with celiac disease bind to thyroid follicles and extracellular matrix and may contribute to thyroid dysfunction

Background: Individuals with active celiac disease (CD+) have an increased incidence of thyroid dysfunction, which improves on a gluten-free diet (CD-). We investigated whether tissue transglutaminase-2 IgA antibodies (anti-TGase II) present in sera of patients with celiac disease react with thyroid tissue and possibly contribute to thyroid disease. Methods: Serum from 40 active celiac patients taken before a gluten-free diet (CD+), 46 patients on a gluten-free diet (CD-), 40 normal controls (NC), and 25 with Crohn's disease (CROHN) was used. All sera were screened for antithyroperoxidase antibodies (TPO-AB) and thyroglobulin antibodies (TG-AB), and indirect immunofluorescence (IIF) was performed on primate thyroid tissue sections using TPO-AB- and TG-AB-negative sera. Results: IIF with thyroid seronegative, anti-TGase II-positive CD+ sera (n = 23) demonstrated staining of thyroid follicular cells and extracellular matrix, in an identical pattern with monoclonal anti-human TGase II antibody. Evidence of TGase II as the antigen in thyroid tissue was supported by elimination of the IIF pattern when sera were depleted of anti-TGase II by pretreatment with human recombinant TGase II. No staining of thyroid tissue was observed when sera from CD+ patients that were negative for TGase II antibodies, or sera from NC subjects were used. Thyroid antibodies were found in 43% of CD+ patients, significantly higher than NC and CROHN patients (p < 0.0001). In addition, a positive correlation was observed between anti-TGase II and TPO-AB titers (p = 0.0001; r = 0.63). Conclusions: Anti-TGase II antibodies bind to TGase II in thyroid tissue, and titers correlate with TPO antibody titers. These findings suggest that anti-TGase II antibodies could contribute to the development of thyroid disease in celiac disease.