Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Antonelli, Alessandro; Fallahi, Poupak; Elia, Giusy; Ragusa, Francesca; Paparo, Sabrina Rosaria; Ruffilli, Ilaria; Patrizio, Armando; Gonnella, Debora; Giusti, Claudia; Virili, Camilla; Centanni, Marco; Shoenfeld, Yehuda; Ferrari, Silvia Martina
• Is Part Of: Best practice & research. Volume 34:Issue 1(2020)
• Publication Date: 2020-01
• Subjects: Graves' disease -- Graves' ophthalmopathy -- CXCR3 -- CXCL10 -- Th1 immune response -- teprotumumab; Endocrine glands -- Diseases -- Periodicals; Metabolism -- Disorders -- Periodicals; Endocrinology -- Periodicals; Metabolism -- Periodicals; 616.4
• DOI: 10.1016/j.beem.2020.101388
• Languages: English
• ISSNs: 1521-690X

Abstract

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 (C-X-C)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.