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Immunoglobulin G Antithyroid Peroxidase Antibodies in Hashimoto’s Thyroiditis: Epitope-Mapping Analysis¹

Department of Biochemistry, Medical Center of Postgraduate Education (B.C., M.J.-.B.), Marymoncka 99, Warsaw 01 813, Poland; the Department of Medicine, University of Sheffield Clinical Sciences Center, Northern General Hospital (R.S.M., M.S.A., P.F.W., E.H.K., A.P.W.), Sheffield, United Kingdom S5 7AU; and Faculté de Médicin, Laboratoire de Biochimie Endocrinienne et Metabolique (P.C.), Marseille, France

Address all correspondence and requests for reprints to: Prof. A. P. Weetman Department of Medicine, University of Sheffield Clinical Sciences Center, Northern General Hospital, Sheffield, United King-dom S5 7AU.

Patients with autoimmune thyroid disease frequently have high affinity antibodies to thyroid peroxidase (TPO), although the role they play in disease pathogenesis is not known. We have previously prepared 37 monoclonal anti-TPO IgG Fab fragments from two patients with Hashimoto’s thyroiditis and demonstrated the similarity of these Fab sequences to those published previously, mainly derived from patients with Graves’ disease. In this paper, we describe epitope mapping of these Fabs using a previously characterized panel of murine monoclonal antibody (mAb) and show that the Fabs bind to two neighboring epitopes on native TPO. Although the epitope-mapping method differs from that used to characterize previously published TPO-reactive Fab sequences, it indicates a similarly restricted response to neighboring epitopes in both Graves’ disease and Hashimoto’s thyroiditis. The epitope mapping included mAb 47, which binds to a linear TPO peptide of known sequence in addition to native TPO. Although TPO-reactive Fab did not inhibit the binding of mAb 47, mAb 47 did inhibit the binding of Fab, indicating the likely site of the immunodominant region on native TPO. These results confirm the restricted nature of TPO antibody and further delineate the immunodominant region of native TPO as defined by the mAb.

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