Introduction: 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.
Methods: 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.
Results: 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.
Conclusions: 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.