Li Yi, Lee Pui Y, Sobel Eric S, Narain Sonali, Satoh Minoru, Segal Mark S, Reeves Westley H, Richards Hanno B
Division of Rheumatology & Clinical Immunology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0221, USA.
Arthritis Res Ther. 2009;11(1):R6. doi: 10.1186/ar2590. Epub 2009 Jan 14.
The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was to determine whether expression of Fc receptor (FcgammaR) I on circulating monocytes is associated with systemic inflammation and renal disease in SLE patients.
We studied 205 SLE patients (132 with LN and 73 without LN) along with 74 healthy control individuals. Surface expression of CD14 (monocytes), FcgammaRI/CD64, FcgammaRII/CD32, and FcgammaRIII/CD16 was evaluated by flow cytometry. Monocyte function was assessed by determining the migratory capacity and the ability to produce CCL2 (monocyte chemotractic protein 1). High-sensitivity C-reactive protein, C3 and C4 were measured by nephelometry.
There was little difference in the expression of FcgammaRIII/CD16 or FcgammaRIII/CD32 on circulating monocytes between patients with SLE and control individuals. In contrast, FcgammaRI/CD64 expression was significantly higher in SLE patients and even higher in patients with LN. FcgammaRI/CD64 expression was positively associated with serum creatinine and indicators of systemic inflammation. Monocytes from patients with high FcgammaRI/CD64 expression also exhibited increased chemotaxis and capacity to produce monocyte chemotractic protein 1.
Increased FcgammaRI/CD64 expression on circulating monocytes parallels systemic inflammation and renal disease in SLE patients. We propose that circulating monocytes activated by immune complexes and/or proinflammatory mediators upregulate surface expression of FcgammaRI/CD64 in SLE. The enhanced chemotactic and inflammatory potential of the activated monocytes may participate in a vicious cycle of immune cell recruitment and renal injury in SLE.
IgG Fcγ/CD64的高亲和力受体对狼疮性肾炎（LN）的发展至关重要。含IgG的免疫复合物使募集的单核细胞上的Fc受体交联是系统性红斑狼疮（SLE）中免疫复合物介导的肾炎的关键步骤。本研究的目的是确定循环单核细胞上Fc受体（FcγR）I的表达是否与SLE患者的全身炎症和肾脏疾病相关。
我们研究了205例SLE患者（132例有LN，73例无LN）以及74名健康对照个体。通过流式细胞术评估CD14（单核细胞）、FcγRI/CD64、FcγRII/CD32和FcγRIII/CD16的表面表达。通过测定迁移能力和产生CCL2（单核细胞趋化蛋白1）的能力来评估单核细胞功能。通过散射比浊法测量高敏C反应蛋白、C3和C4。
SLE患者和对照个体的循环单核细胞上FcγRIII/CD16或FcγRIII/CD32的表达几乎没有差异。相反，FcγRI/CD64表达在SLE患者中显著更高，在LN患者中甚至更高。FcγRI/CD64表达与血清肌酐和全身炎症指标呈正相关。FcγRI/CD64表达高的患者的单核细胞也表现出趋化性增加和产生单核细胞趋化蛋白1的能力增强。
循环单核细胞上FcγRI/CD64表达增加与SLE患者的全身炎症和肾脏疾病平行。我们提出，在SLE中，由免疫复合物和/或促炎介质激活的循环单核细胞上调FcγRI/CD64的表面表达。活化单核细胞增强的趋化和炎症潜能可能参与SLE中免疫细胞募集和肾损伤恶性循环。
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