CSF2 and autoimmune disease: TNF-α, a gene located in the HLA class 3 region, plays an essential role in the pathology process of inflammation and autoimmune disorders.[8,42] A large number of literatures have demonstrated the fluctuating TNF-α concentration in both the plasma and synovial fluid of juvenile with chronic arthritis.[43–45] The fluctuation in levels of TNF-α would affect the levels of multiple cytokines, including IL-1β, IL-6, IL-8, MCP-1, GM-CSF, and CCL5 [46] as well as several matrix metalloproteinase.[47] These cytokines were further involved in the progression of joint destruction in JIA.