While the role of proinflammatory cytokines, such as interleukin-1(IL-1), interleukin-6(IL-6), and tumor necrosis factor-α (TNF-α), in the pathogenesis of RA has been well-established, the contribution of the immunoglobulin G subclass IgG4 remains a topic of ongoing investigation. The gene discussed is TNF; the disease is rheumatoid arthritis.