| Background:Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with abnormally activated immune response. As we known, both T- and B-lymphocyte hyperreactivity contribute to lupus pathology which result in tissues and cells damage by deposition of pathogenic autoantibodies and immune complexes. However, the cause of SLE has not been clearly established.Interferon alpha (IFN-a), as a fundamental mechanism, through which the immune system is kept in balance, also plays an important role in the onset and progression of lupus. It is also strongly correlated with SLE activity index (SLEDAI) and disease severity. Lynda et al detected increased levels of IFN-a by ELISA in 50% patients, whereas microarray analysis revealed that 96% patients upregulated expression of the typeâ… interferon-inducible gene. Several factors may contribute to the lower sensitivity of the IFN serum assay(s). SLE patients, for example, have been shown to display anti-IFN antibodies in their serum that may interfere with ELISA measurements. Additionally, the antibodies used for ELISA detection may not react with all the IFN species that may circulate in the blood for the inherent insensitivity and unreliability of ELISA. So it is necessary to identify proteins on the cell surface that can be used clinically to assess IFN-a levels rapidly and reliably and that may be well suited to monitor disease activity.Recently, using microarray and real-time polymerase chain reaction (PCR) to analyse peripheral blood mononuclear cells (PBMCs) from lupus patients has demonstrated increased expression of a broad spectrum of IFN-inducible genes(OAS2, OASL, IFIT1, IFIT4, STAT1, ISG15, MX1, MX2, PLSCR1, XIAPaf1 and IRF7), a feature associated with active disease, renal involvement, and the production of autoantibodies against DNA-protein and RNA-protein autoantigens.Interferon-induced protein 44 (IFI44), namely p44, is a new member of the interferon-induceble gene family. It was originally found in microtubular aggregates in hepatocytes of non-A, non-B (NANB) virus-infected chimpanzees. The human p44 gene spans approximately 14 kbp of DNA and is consisted of nine exons separated by eight introns. There is an interferon-stimulated response element in the promoter sequence. IFI44 is a cytoplasmic protein and is associated with microtubular structures. With antiproliferative activity, it has been strongly implicated in activation of innate immunity system, the IFN signal transduction pathway and cell-mediated immunity imbalance. Because of its specificity in SLE, IFI44 gene has attracted several reseachers' attention. Since the measurement of IFI44 gene is expesively and time consuming, we aim to identify a biomarker for IFN-I activity in clinical samples for monitoring disease activity.Antibodies are naturally potent inducers of inflammation. As secondary products of the abnormal immunity, they have often been seen primary mediators of the organ damage. Several findings suggest that there is a relationship between binding and penetration of autoantibodies in the different cell types and the initiation of events leading to various functional cellular alterations. The mechanisms by which antibodies penetrate the cell membrane are still very obscure. Recent findings supposed that CD64 constitutes one of the main effector mechanisms through which autoantibodies exert their action.FcyRs are one kind of receptors which are expressed on human peripheral blood mononuclear cells. FcyRI/CD64, for instance, is a high-affinity IgG receptor constitutively expressed at the surface of monocytes. Recently it was reported that CD64 expression on monocytes can be used to aid in the diagnosis of infections. Dysregulated CD64 expression may have functional consequences, as this activating FcyR plays important roles in phagocytosis, cytolysis, and induction of inflammatory cytokines. It is of great importance to control the autoimmunity-tolerance balance in the periphery which provides evidence of its contribution to the onset of SLE.Whether CD64 activation is related to IFI44 expression in peripheral blood monouclear cells from SLE, however, it is unknown. Can CD64 be a surrogate marker for IFI44 in clinical samples?Objective:To investigate the expression levels of gene IFI44 and CD64 in eperipheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) and to correlate their expression levels. To identify a surrogate marker for IFN-a activity in clinical samples for monitoring disease activity and response to therapy.Methods:Peripheral blood cells were drawed from 18 SLE patients and 12 normal controls with total RNA extracted and reversely transcribed into complementary DNA. Gene expression levels were measured by realtime polymerase chain reaction, being standardized to a housekeeping gene. The data were analyzed using SPSS 13.0 for Windows. Comparisons between groups were conducted using the Mann-Whitney U test or the Independent-Samples T test. Correlation between groups was evaluated using the Spearman test. P values less than 0.05 were considered significant.Results:The expression level of gene IFI44 and gene CD64 in SLE patients were significantly higher than those in normal controls respectively (Z=-2.455, P=0.013; Z=-2.942, P=0.002). There is positive correlation of transcription level between gene IFI44 and gene CD64(r=0.845, P<0.001).Conclusion:The expression levels of IFI44 and CD64 in SLE patients were significantly up-regulated, indicating their roles in the pathogenesis of SLE. IFI44 correlated highly with CD64. Flow-cytometry analysis of CD64 may reveal IFI44 expression level and the activation of type I interferon, which contribute to the onset and progress of SLE and are associated with disease activity. According to this base, CD64 may be well suited to monitor disease activity and to help us to choose the best teatment for SLE patients. |
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