In RA, the unique top canonical pathways included iCOS-iCOSL signaling in T helper cells, Regulation of IL-2 expression in activated and anergic T lymphocytes, CD28 signaling in T helper cells, T cell receptor signaling and PKCθ signaling in T lymphocytes, reflecting the crucial role of T cells in the RA pathogenesis. The gene discussed is ICOSLG; the disease is rheumatoid arthritis.