Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease characterized by excessive production of type Ι IFNs, autoantibodies and immune complexes causing different organ damage. SLE is associated with a defect in self tolerance due to dysregulated innate and adaptive immune cells. The breakdown of tolerance to nuclear antigens, especially nucleic acids, result in widespread organ damage. Type Ι IFN affects the immunological roles of immune cells especially monocytes, T cells and B cells that are involved in the loss of tolerance and autoimmunity in SLE. Environmental factors are suggested to be responsible for the induction of SLE disease in genetically susceptible individuals. In this study, the potential differential expression of representative genes for the three type I IFN modules (RSAD2 from M1.2, GBP1 from M3.4 and IRF9 from M.12) were investigated and their association with monocytes and T-cell subtypes differentiation and SLE manifestations was evaluated. The results showed that the three genes are not significantly correlated with monocytes. There is no significant correlation between RSAD2, GBP1 and IRF9 and T-cell subtypes, although a moderate correlations is found only between IRF9 and Treg. GBP1 and IRF9 are significantly associated with joint pain manifestation in SLE patients. Conclusion: GBP-1 and IRF9 can be utilized as biomarkers for joint pain in SLE.