Increased expression of FcgammaRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus.

Abstract

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.

• Authors: Yi Li, Pui Y Lee, Eric S Sobel, Sonali Narain, Minoru Satoh, Mark S Segal, Westley H Reeves, Hanno B Richards
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 11 Issue 1 Pg. R6 ( 2009) ISSN: 1478-6362 [Electronic] England
• PMID: 19144150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigen-Antibody Complex
• Biomarkers
• FCGR1A protein, human
• FCGR3B protein, human
• Fc gamma receptor IIA
• GPI-Linked Proteins
• Receptors, IgG

Topics

• Adult
• Antigen-Antibody Complex (blood, immunology, metabolism)
• Biomarkers (blood)
• Chemotaxis, Leukocyte (immunology)
• Flow Cytometry
• GPI-Linked Proteins
• Humans
• Inflammation (blood, immunology, metabolism)
• Kidney Function Tests
• Leukocytes, Mononuclear (immunology, metabolism)
• Lupus Nephritis (blood, immunology, physiopathology)
• Male
• Receptors, IgG (blood, immunology, metabolism)
• Up-Regulation