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Paul Hobby, Andrzej Gardas, Roman Radomski, Alan M. McGregor, J. Paul Banga, Brian J. Sutton, Identification of an Immunodominant Region Recognized by Human Autoantibodies in a Three-Dimensional Model of Thyroid Peroxidase, Endocrinology, Volume 141, Issue 6, June 2000, Pages 2018–2026, https://doi.org/10.1210/endo.141.6.7506
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Abstract
Autoimmune thyroid diseases (AITD) are characterized by the presence of autoantibodies to thyroid peroxidase (TPO). This response is dominated by autoantibodies to two conformational determinants, termed A and B, that have been defined by monoclonal antibodies but whose structures and location within TPO are unknown. We have modeled the three-dimensional structure of the extracellular region of TPO, raised antisera to prominent surface structures, and identified an epitope that we show to be a critical part of the B determinant. Antibodies to this epitope inhibit the binding to TPO of human autoantibodies in virtually all serum samples from 65 patients with AITD that were tested. This first description of a model of the three-dimensional structure and location of a major autoantigenic determinant within the TPO molecule may provide structural clues for identifying causative agents or developing novel therapeutic strategies.