Introduction: Rheumatic diseases are inflammatory diseases that damage target organs via multiple subsets of immune cells. Fractalkine (FKN) acts as chemoattractant as well as adhesion molecule. It contributes to the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases through multiple mechanisms: the migration of monocytes and cytotoxic effector T cells, the proliferation and activation of fibroblast-like synoviocytes, angiogenesis, and osteoclastogenesis. FKN has potential as a new therapeutic target, and clinical trials on anti-FKN monoclonal antibodies for RA are ongoing. FKN-targeted therapy has been developed and a humanized anti-FKN monoclonal antibody is currently being tested in phase 2 clinical trials. Areas covered: This review summarizes accumulated evidence on the involvement of FKN in RA and other rheumatic diseases, including systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis, Sjögren's syndrome (SS), osteoarthritis, and systemic vasculitis. Expert opinion: A phase 1/2a clinical trial on anti-FKN demonstrated its safety, tolerability, and clinical efficacy. Anti-FKN therapy has potential in the treatment of atherosclerosis and interstitial lung diseases associated with RA. Based on recent findings, other rheumatic diseases, including SLE, polymyositis/dermatomyositis, and SS, may also be treated using anti-FKN therapy.
Keywords: CX3CR1; fractalkine; polymyositis/dermatomyositis; rheumatoid arthritis; sjögren’s syndrome; systemic lupus erythematosus; systemic sclerosis; systemic vasculitis.