Interferon-inducible systemic lupus associated gene, IFIT1 in systemic lupus erythematosus patients

ABSTRACT

Systemic lupus erythematosus [SLE] is a prototype of human systemic autoimmune diseases. Although the definite etiopathogenesis of SLE remains unclear, many different mechanisms may contribute to the pathogenesis of SLE. Interferons [IFNs] are important immune system mediators that could impact the initiation or amplification of autoimmunity and tissue damage through their diverse actions on dendritic cells. T, B lymphocytes, natural killer cells, and mononuclear phagocytes. Recent studies suggest an important role of interferon alpha in the immunopatahogenesis of SLE. Data demonstrating a correlation between IFN alpha and SLE range from elevated IFN alpha level in patients serum and induction of interferon regulated genes in peripheral blood mononuclear cells to drug induced lupus in hepatitis C or cancer patients treated with recombinant IFN alpha. In the present work we studied the mRNA expression level of the interferon-inducible with tetratricopeptide repeats 1 [IFIT1] gene using Real-time PCR to examine the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of type 1 interferon pathway. Expression of IFIT1 gene was significantly higher in SLE when compared to the control group and the level of expression showed a positive correlation with disease activity index. Renal affection was more frequently encountered in SLE patients with IFIT1 overexpression. The gene expression profiles seems to be the molecular basis of the diverse immune phenotype of SLE. Defining the nature of the major IFNs or other factors, that drive the IFN-regulated gene expression noted in SLE is an important area of investigation that may lead to new approaches to targeted therapy of SLE