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  • Title: Identification of an immunodominant region recognized by human autoantibodies in a three-dimensional model of thyroid peroxidase.
    Author: Hobby P, Gardas A, Radomski R, McGregor AM, Banga JP, Sutton BJ.
    Journal: Endocrinology; 2000 Jun; 141(6):2018-26. PubMed ID: 10830285.
    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.
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