Evolution of the views on pathogenesis of autoimmune thyroid diseases and prospects for their target therapy

Abstract

Modern scientific literature contains few reports concerning the influence of target therapy on pathogenetic factors of autoimmune thyroid diseases (AITD). Despite a large number of hypotheses of AITD pathogenesis, the only well established fact is the starting stage of Graves disease (GD) and autoimmune thyroiditis (AIT) is the loss of tolerance to thyroid autoantigens and the final stage is production of autoantibodies to them. Up to 75-80% of the patients with GD have antibodies against thyroid peroxidase and only few of them have anti-thyroglobulin antibodies more characteristic of AIT. Thyrotropin releasing hormone (TRH) is known to stimulate T-lymphocyte production via local effect on insulin-like growth factor (IGF). Modern studies confirm the important role of cytokines in immunopathogenesis of GD and AIT. Moreover, excess activation of this system in AITD provides a basis for the development of specific therapeutic approaches to personified pharmacotherapy. The effectiveness of anti-cytokine therapy of GD and AIT was demonstrated in animal experiments. Studies of therapy targeted on orbital and thyroid autoantigens in AITD are currently underway. The existence of specific receptors and the ability of immunocompetent cells to produce neuropeptides create prerequisites for their participation in intercellular cooperative processes. It can be supposed, by analogy with the influence of hormones and neuromediators on immunocytes, that neurohormones act on them via specific receptors with the involvement of cyclic nucleotides. It opens up opportunity for targeted correction of these relationships. Further studies of immunopathogenetic mechanisms of GD and AIT for better understanding the role of interaction between inborn and acquired immunity, its regulation, and intersystem transmission of signals in the development of these diseases are needed to realize modern strategies of their target therapy.