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Pendrin Is a Novel Autoantigen Recognized by Patients with Autoimmune Thyroid Diseases

Division of Regenerative Medicine and Therapeutics (A.Y., I.H., Y.S., Y.Y., J.M.) Department of Genetics and Regenerative Medicine, Tottori University Graduate School of Medicine, Yonago, Tottori 683–8504, Japan; First Department of Internal Medicine (S.T., T.O., O.I., C.S.), Tottori University Faculty of Medicine, Yonago, Tottori 683-8504, Japan; Department of Bioregulation (T.A., K.S.), National Institute of Infectious Diseases, Tokyo 189-0002, Japan; Kamijo Thyroid Research Institute (K.K.), Sapporo 064-0822, Japan; Division of Clinical Immunology (S.I.), Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan; and Department of Pathology (P.C.), Johns Hopkins University, Baltimore, Maryland 21205

Address all correspondence and requests for reprints to: Dr. Akio Yoshida, Division of Regenerative Medicine and Therapeutics, Department of Genetics and Regenerative Medicine, Tottori University Graduate School of Medicine, Nishimachi 36-1, Yonago, Tottori 683-8504, Japan. E-mail: ayoshida{at}grape.med.tottori-u.ac.jp.

Context: Pendrin is an apical protein of thyroid follicular cells, responsible for the efflux of iodide into the follicular lumen via an iodide-chloride transport mechanism. It is unknown whether pendrin is recognized by autoantibodies.

Objective: Our objective was to examine the prevalence of pendrin antibodies in autoimmune thyroid diseases and compare with that of thyroglobulin, thyroperoxidase, TSH receptor, and sodium iodide symporter antibodies.

Design: In a prevalent case-control study, we analyzed the sera of 140 autoimmune thyroid disease cases (100 with Graves’ disease and 40 with Hashimoto’s thyroiditis) and 80 controls (50 healthy subjects, 10 patients with papillary thyroid cancer, 10 with systemic lupus erythematosus, and 10 with rheumatoid arthritis). Pendrin antibodies were measured by immunoblotting using extract of COS-7 cells transfected with pendrin and a rabbit polyclonal pendrin antibody.

Results: Pendrin antibodies were found in 81% of the cases and 9% of controls (odds ratio = 44; P < 0.0001). Among cases, pendrin antibodies were more frequent and of higher titers in Hashimoto’s thyroiditis than in Graves’ disease. Pendrin antibodies correlated significantly with thyroglobulin, thyroperoxidase, and sodium iodide symporter antibodies but not with TSH receptor antibodies. Pendrin antibodies were equally effective as thyroglobulin and thyroperoxidase antibodies in diagnosis of autoimmune thyroid diseases, especially Hashimoto’s thyroiditis.

Conclusions: The study identifies pendrin as a novel autoantigen recognized by patients with autoimmune thyroid diseases and proposes the use of pendrin antibodies as an accurate diagnostic tool.