Immunological Aspects of Graves’ Ophthalmopathy

Abstract

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity.

Protein tyrosine phosphatase 1B as a therapeutic target for Graves’ orbitopathy in an in vitro model

“…TLRs participate in autoimmune diseases [ 18 ] and TLR-related signaling activates NF-κB to secrete inflammatory cytokines [ 19 ]. After transfection of GO and non-GO fibroblasts with siPTPN1 for 24 hours, TLR2, 4, and 9 mRNA expression levels were identified through RT-PCR analysis.…”

Bisphosphonate-Induced Acute Orbital Inflammation in a Patient With Underlying Thyroid Ophthalmopathy

“…In Graves’ orbitopathy, TSH receptor antibodies and activated T-cells also play important roles [ 6 ]. The autoimmune process by TSH receptor antibodies induce retro-ocular adipogenesis, an inflammatory infiltrate, and glycosaminoglycan (GAG) accumulation [ 7 ]. Increased activity of T-cells also plays a role in the development of orbitopathy by Th1 lymphocyte-producing cytokines-induced fibroblast proliferation and GAG production, as well as by Th2 lymphocyte remodeling and fibrosis of periorbital tissues in the late phase [ 7 ].…”

“…The autoimmune process by TSH receptor antibodies induce retro-ocular adipogenesis, an inflammatory infiltrate, and glycosaminoglycan (GAG) accumulation [ 7 ]. Increased activity of T-cells also plays a role in the development of orbitopathy by Th1 lymphocyte-producing cytokines-induced fibroblast proliferation and GAG production, as well as by Th2 lymphocyte remodeling and fibrosis of periorbital tissues in the late phase [ 7 ]. Considering how both mechanisms involve T-cell and cytokine release, it is possible that underlying Graves’ orbitopathy can promote bisphosphonate-induced orbital inflammation.…”

MicroRNAs and Autoimmune-Mediated Eye Diseases

“…Its clinical manifestations include exophthalmos, eyelid retraction, strabismus, and exposure keratitis, which may cause cosmetic and functional deficits ( Dik et al, 2016 ). Although the precise pathophysiology of GO remains unclear, increasing evidence has shown this disease may result from the autoimmune reactions in which the sensitive T cells as well as autoantibodies against common antigens [including thyrotropin receptor (TSHR), insulin-like growth factor-1 receptor, thyroglobulin, calsequestrin (CASQ1) and collagen XIII] contribute to the activation and proliferation of orbital fibroblasts (OFs), resulting in extraocular tissues edema and fibrosis ( Lahooti et al, 2010 ; Bahn, 2015 ; Shanmuganathan et al, 2015 ; Lacheta et al, 2019 ). Recently, particular attention has been paid to the role of miRNAs in the pathogenesis of GO.…”