| Research background and ObjectivesSystemic lupus erythematosus (SLE) is a multisystem inflammatory and autoimmune disease. Despite the etiology of SLE has not been fully understood, the abnormal lymphocyte apoptosis, decreased clearance of activated T cells and involvement of multiple cytokines including IFN-y, interleukin (IL)-10and IL-6have been demonstrated with the pathogenesis of SLE. Apolipoprotein (apo) E is a multifunctional glycoprotein synthesized chiefly by the liver and the macrophage. It’s implicated in human lipoprotein metabolism and cardiovascular disease. It has been reported that apoE deficient lupus mouse models present with accelerated atherosclerosis, and the intermediate density lipoprotein (IDL) fraction, which is the most strongly, significantly, and positively correlated with intima-media thickness (IMT), is significantly modulated by the apoE genotype. Recently, increasing studies have proved that apoE has anti-inflammatory and immunoregulatory effects. It plays a key role in inhibiting the proliferation of T lymphocytes, regulating immune reactions and interacting with several cytokines. Moreover, it has been suggested that apoE might play a pivotal role in modulating inflammatory and immune response in autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis. These lines of evidence suggest that apoE may play an important role in the pathogenesis of SLE. To investigate the expression of apoE in the Peripheral blood and serum of patients with systemic lupus erythematosus (SLE) and its role in SLE, including its relationship with disease activity, anti-dsDNA, interleukin(IL)-6, IL-10and IFN-y.Methods76cases with SLE (4males and72females) and40age-and sex-matched healthy controls were studied. SLE patients were divided into two groups according to disease activity:inactive group when SLEDAI≤4(28cases) and active group when SLEDAI>4(48cases). Peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation. Real time-PCR technique was used to analyze the expression of apoE mRNA. The serum levers of apoE, IL-6, IL-10and IFN-y were measured by ELISA.ResultsComparison of apoE mRNA expressions in SLE patients and controlsCompared with healthy controls, the relative expression levels of apoE transcripts in active SLE patients were increased3.32-fold in active status (P<0.01). There was no significant difference for apoE between inactive SLE group and the healthy subject group.Sera apoE and cytokines levels in SLE patients and healthy controlsThe serum levels of apoE, IL-6, IL-10and IFN-y in active SLE patients were increased significantly than those in healthy controls (P=0.001,0.007,0.013,0.005). No significant differences of apoE, IL-6, IL-10and IFN-γ were found between stable SLE patients and controls (P>0.05).Comparison of sera apoE levels in LN patients and lupus non-nephritis patientsThe apoE concentrations in LN and lupus non-nephritis patients were both higher than healthy group. There was no difference between LN group and lupus non-nephritis group (P>0.05).Correlations of apoE and IL-6with indicators for disease activity of SLEThe serum concentrations of apoE showed a significant positive correlation with SLEDAI scores and anti-dsDNA (r=0.761,0.658; P<0.01), and so did IL-6(r=0.693,0.525; P<0.01).Correlations of sera apoE levels with cytokines and blood lipid levels in SLE patientsApoE protein expression had a close correlation with IL-6,IL-10and IFN-γ (r=0.893,0.738,0.755; P<0.01) and no association with the mean concentration of total cholesterol(TC) and triglyceride(TG)(P>0.05).Conclusions1. The expressions of apoE protein and mRNA in SLE patients are up-regulated in active SLE patients and not constitutively expressed in health subjects.2. There is no difference for apoE in LN and lupus non-nephritis.3. ApoE positively correlated with disease activity of SLE, IL-6, IL-10and IFN-y. It may takes a relative important role in the onset of SLE by interacting with IL-6, IL-10and IFN-γ... |
