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Ann Rheum Dis. Dec 2005; 64(12): 1692–1697.
Published online Apr 20, 2005. doi:  10.1136/ard.2004.033753
PMCID: PMC1755300
Type I interferon correlates with serological and clinical manifestations of SLE
M Dall'Era, P Cardarelli, B Preston, A Witte, and J Davis
University of California, San Francisco, San Francisco, CA 94143, USA.
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems triggered by the production of autoantibodies. Previous clinical studies in humans and murine models suggest that type I interferons (IFNs) are important for the initiation and potentiation of SLE activity.
Methods: 65 consecutive patients with SLE were identified from the University of California, San Francisco Lupus Clinic with moderate-severe disease activity. 94 serological samples were collected. Type I IFN levels and the ability of plasma to induce expression of several surface markers of dendritic cell maturation were measured.
Results: Type I IFN levels correlated with the presence of cutaneous manifestations, and there was a trend towards correlation with renal disease. No correlation was found between type I IFN levels and neurological disease. Type I IFN levels correlated positively with the SLEDAI score and anti-dsDNA levels and inversely with C3 levels. Interestingly, type I IFN levels were highest in African American patients. SLE plasma also induced the expression of MHC class I, CD38, and CD123 on monocytes, and was blocked by the addition of a monoclonal antibody to IFNAR1.
Conclusions: The pathogenic role of type I IFN is suggested by the induction of cell surface markers for dendritic cell maturation. The potential therapeutic utility of antibodies directed to either type I IFN or IFNAR1/IFNAR2 may be of interest in further studies.
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Figures and Tables
Figure 1
Figure 1
 The human hepatoma cell line Hil3, transfected with ISRE-Luc, responds to type I IFN stimulation in a dose dependent manner. Luciferase activity is measured in counts per second and is proportional to IFN activity as demonstrated by linear regression (more ...)
Figure 2
Figure 2
 Type I IFN activity in the Hil3 ISRE-Luc reporter assay is neutralised by mouse anti-IFNAR1 (64G12) in a dose dependent manner. A fixed concentration of IFN (100 U/ml) is added to cells in the presence of a dose titration of IFNAR1 specific (more ...)
Figure 3
Figure 3
 IFN correlated significantly with the presence of skin disease (median 3.138 U/ml v 1.022 U/ml, p = 0.0002). There was a trend towards a positive correlation between IFN and the presence of renal disease (median 2.072 U/ml v 1.193 U/ml, p = (more ...)
Figure 4
Figure 4
 IFN levels correlated positively with SLEDAI scores (rs = 0.451, p = 0.0002), ESR (rs = 0.481, p = 0.0002), and anti-dsDNA (rs = 0.509, p = 0.000). IFN levels correlated negatively with C3 levels (rs = –0.591, p = 0.000).
Figure 5
Figure 5
 Anti-IFNAR blockade of recombinant IFNα mediated dendritic cell development. Monocyte differentiation was monitored by increased expression of the cell surface markers MHC class I, CD123, and CD38. Normal healthy donor plasma does not (more ...)
Figure 6
Figure 6
 Anti-IFNAR blockade of SLE plasma mediated DC development. Monocytes isolated from healthy donor PBMCs differentiate in response to IFN stimulation. This maturation process is monitored by up regulation in the expression of cell surface markers (more ...)
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