[HTML][HTML] Increased expression of FcγRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus

Y Li, PY Lee, ES Sobel, S Narain, M Satoh… - Arthritis research & …, 2009 - Springer
Y Li, PY Lee, ES Sobel, S Narain, M Satoh, MS Segal, WH Reeves, HB Richards
Arthritis research & therapy, 2009Springer
Introduction The high-affinity receptor for IgG Fcγ/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 (FcγR) 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 …
Introduction
The high-affinity receptor for IgG Fcγ/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 (FcγR) 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), FcγRI/CD64, FcγRII/CD32, and FcγRIII/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 FcγRIII/CD16 or FcγRIII/CD32 on circulating monocytes between patients with SLE and control individuals. In contrast, FcγRI/CD64 expression was significantly higher in SLE patients and even higher in patients with LN. FcγRI/CD64 expression was positively associated with serum creatinine and indicators of systemic inflammation. Monocytes from patients with high FcγRI/CD64 expression also exhibited increased chemotaxis and capacity to produce monocyte chemotractic protein 1.
Conclusions
Increased FcγRI/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 FcγRI/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.
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