Graves' disease: clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy

Graves' disease: clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy:



Publication date: Available online 4 February 2020

Source: Best Practice & Research Clinical Endocrinology & Metabolism

Author(s): Alessandro Antonelli, Poupak Fallahi, Giusy Elia, Francesca Ragusa, Sabrina Rosaria Paparo, Ilaria Ruffilli, Armando Patrizio, Debora Gonnella, Claudia Giusti, Camilla Virili, Marco Centanni, Yehuda Shoenfeld, Silvia Martina Ferrari

Abstract

Graves’ disease (GD) is characterized by thyrotoxicosis, caused by the presence of circulating thyroid stimulating antibodies (TSAb), that are determinant also in the pathogenesis of its extrathyroidal manifestations [Graves’ ophthalmopathy (GO), pretibial myxedema]. T helper (Th)1 immune response prevails in the immune-pathogenesis of GD and GO, during the active phase, when Th1 chemokines, and their (CXC)R3 receptor, play a key role. In GD, the existing treatments are not ideal for hyperthyroidism (long-term remission with anti-thyroid-drugs only in 50% of patients; while radioiodine and surgery cause hypothyroidism). In GD, antigen-specific therapy has been recently published, with the induction of T cell tolerance via an immunization by TSH-R peptides. In GO, rituximab and drugs targeting cytokines have been evaluated. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) showed to be very effective in GO patients.

Further researches are necessary to identify novel effective therapies targeting GD, or GO.