CTLA4 and autoimmune disease: It has been shown that methotrexate may directly or indirectly affect the expression and/or secretion of the various immune response mediators involved in the pathogenesis of JIA and other autoimmune diseases, including cytokines (such as tumour necrosis factor alpha (TNFα), interleukin 1 (IL1), IL2, IL6, IL10), nuclear factor kappa B (NFκB), cytotoxic T-lymphocyte associated protein 4 (CTLA4) and others [10–13].