Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a systemic disorder characterized by the infiltration of IgG4-positive plasma cells and elevated serum IgG4 levels. The ocular symptoms of this disease can affect multiple structures, including the lacrimal gland, orbital fat, infraorbital nerves, extraocular muscles, and eyelids.These manifestations are often accompanied by inflammatory and fibrotic processes. At the molecular level, IgG4-ROD is linked to the interaction of various immune cells and cytokines. These include T helper cell 1 (Th1), T helper cell 2 (Th2), regulatory T cells (Tregs), and follicular helper T cells (Tfh), along with cytokines interleukin 4 (IL-4), interleukin 13 (IL-13), and transforming growth factor-β (TGF-β). They promote B cell activation and IgG4 production, and also facilitate the development of fibrosis. Diagnosis of IgG4-ROD is mainly based on histopathological features. Treatment typically involves the use of glucocorticoids and immunosuppressive agents, which aim to control immune-mediated inflammation and fibrosis, alleviate symptoms, and prevent organ damage. As our understanding of the molecular pathogenesis of IgG4-ROD advances, it is anticipated that treatment strategies will be continuously refined. This will enable us to offer patients more precise and effective therapeutic options, ultimately improving prognosis and quality of life. This article provides a summary and clarification of the key molecules and signaling pathways involved in the pathogenesis of IgG4-ROD. It also reviews, from a molecular perspective, the interplay between autoimmunity and fibrosis, as well as their transformations.
