A GA microsatellite in the Fli1 promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritis

Constructs with variable lengths of the GAn microsatellite in the Fli1 promoter were generated and analyzed in promoter/reporter (P/R) assays in a human T cell line. Using three SLE patient cohorts and matched controls, microsatellite length was measured and association with the presence of disease and the occurrence of specific disease manifestations was assessed.P/R assays demonstrated that the presence of a shorter microsatellite resulted in higher Fli1 promoter activity. A significant association was observed in the lupus cohort SLE in Gullah Health (SLEIGH) between the GA26 base pair allele and absence of nephritis.This study demonstrates that a GAn microsatellite in the human Fli1 promoter is highly polymorphic. The length of the microsatellite is inversely correlated to Fli1 promoter activity in a human T cell line. Although no association between microsatellite length and lupus was observed, an association between a specific microsatellite length and patients without nephritis in the SLEIGH cohort was observed.Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of autoantibodies, formation of immune complexes and subsequent deposition in target tissues with resultant local inflammation and organ damage [1]. Nearly every organ system can be involved in lupus with the most prominent being the kidneys, joints, skin and brain [1]. The major determinant of morbidity and mortality is renal involvement, although infection and cardiovascular disease are leading causes of death. The American College of Rheumatology outlines the most common disease outcomes of SLE in the 1997 revised classification criteria including arthritis, serositis, nephritis, immune-mediated cytopenias, and lupus-specific autoantibody positivity. Commonly, the course of disease will include periods of remission and flares and the disease presentation is heterogeneous among patients making SLE a difficult disease to characterize, diagnose, and st