This is a new application for a YSDRCC pilot/feasibility grant from a clinically trained rheumatologist without NIH fundings who now seeks a financial support to initiate his research in determining Mif gene polymorphisms and cutaneous expression of MIF in patients with systemic lupus erythematosus (SLE). The mucocutaneous system is affected in 85% of patients with SLE. An important concept in the pathogenesis of SLE is that there is an intrinsically heightened state of T lymphocyte responsiveness that contributes to sustained T cell activation and autoantibody production. These events lead to recruitment and activation of inflammatory cells, such as macrophages, and subsequent tissue destruction in inflammatory sites. Several studies showed the requirement of macrophages in the development of murine lupus nephritis, suggesting an important role of macrophages as a pro-inflammatory migration inhibitory factor (MIF) is a pro-inflammatory cytokine secreted from monocytes, macrophages and T cells and has a pivotal, upstream role in activation of macrophages and T cells. Recently, a study identified promoter polymorphisms of the Mif gene that comprises the tetranuclotide repeat sequence (CATT)5-8. In rheumatoid arthritis (RA), a systemic autoimmune disease like SLE, a study showed that patients with RA had a decreased frequency of a single 5-CATT allele (lowest Mif expression), which was even lower in RA patients with mild disease. This suggests a potential role of Mif in the pathogenesis of T cell- and marcrophage-mediated autoimmune inflammatory diseases such as SLE and RA. Of interest, in psoriasis, an increased level of MIF was found in the skin and serum, suggesting a role of MIF in inflammatory skin diseases. Furthermore, a study showed induction of MIF in the skin by UVB, which is a well-known environmental factor for SLE. Based on these observations, a hypothesize that patients with SLE have increased expression of MIF, as a result of genetic pre-disposition, that promotes macrophasge-mediated inflammation and possibly T cell activation will be tested. To investigate this hypothesis, the following will be done. First, define the frequency of low- and high-expression Mif alleles in patients with SLE and correlate them with plasma MIF levels and disease activity. Second, determine the expression of MIF in skin lesions from patients with SLE and discoid lupus.