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.
Naiyer
Afzal J
AJ
Department of Medicine, Celiac Disease Center at Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Shah
Jayesh
J
Hernandez
Lincoln
L
Kim
Soo-Youl
SY
Ciaccio
Edward J
EJ
Cheng
Jianfeng
J
Manavalan
Sanil
S
Bhagat
Govind
G
Green
Peter H R
PH
D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications* / Q000178:diet therapy / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology; D055050:Diet, Gluten-Free; D005109:Extracellular Matrix / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D033862:Iron-Binding Proteins / Q000276:immunology; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013959:Thyroid Diseases / Q000209:etiology* / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D011503:Transglutaminases / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D033862:Iron-Binding Proteins; C000717608:TGM2 protein, human; C006606:anti-thyroglobulin; C056658:TPO protein, human; D007453:Iodide Peroxidase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins