Immunoglobulin G Antithyroid Peroxidase Antibodies in Hashimoto's Thyroiditis: Epitope-Mapping Analysis

Publisher Website
Google Scholar
Abstract
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 pre- pared 37 monoclonal anti-TPO IgGk 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-map- ping method differs from that used to characterize previously pub- lished TPO-reactive Fab sequences, it indicates a similarly restricted response to neighboring epitopes in both Graves' disease and Hashi- moto'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 im- munodominant region of native TPO as defined by the mAb. (J Clin Endocrinol Metab 82: 2639 -2644, 1997)
Keywords

This publication has 0 references indexed in Scilit: