Abstract
Background: Autoimmune thyroid diseases are the most common organ-specific autoimmune diseases. Is established, those diseased as the result of immune systems response on thyroid natural proteins – thyroid peroxidase (TPO), thyreoglobulin and receptor of thyrotrophic hormone. High concentration of specific anti-TPO autoantibodies are present in serum of the patients suffering from Graves\ disease (more than 80%), Hashimotos thyroiditis (more than 90%) and those are specific marker of autoimmune thyroid diseases diagnostic. The definition and study of thyroid antigenic determinants will allow developing new methods of treatment and diagnostic of autoimmune thyroid diseases.
Objectives: The objectives of our study were (i) the computer-aided design of the novel peptides antigenic determinants of the thyroid peroxidase, (ii) in silico modelling of the structural analogs of thyroid peroxidase epitopes peptides, (iii) synthesis of these peptides and (iv) in vitro investigations.
Methods and results: Using program complex designed by authors, we defined one of the antigenic determinants of the thyroid peroxidase. It is formed by amino acid residues Glu734Gln738Asp739Lys741 that are closely spaced on the surface of human TPO. Based on this we make a forecast of the structural analogs of thyroid peroxidase peptide epitopes. Forecast peptides were synthesized by methods classical peptide of chemistry in a solution. In model ELISA system it was shown that one of peptide inhibited binding of anti-TPO autoantibody with immobilized human TPO in the limit 80% when used concentration of peptide equal 1mM.
Conclusions: High activity of forecasting and synthesizing peptide analog of thyroperoxidase antigenic determinant is allowed to use it in development diagnostic systems and therapeutic agents able to modulate immune responses. Using this peptide we develop antigen-coupled absorbent for selective elimination of anti-TPO autoantibodies from serum of the patients suffering from autoimmune thyroid diseases.