Abstract
IntroductionSystemic lupus erythematosus (SLE) is a multi-system autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; thus, there is increasing interest in identifying biomarkers for SLE. In this study we correlated the combined expression level of multiple interferon-inducible chemokines with disease activity, degree of organ damage and clinical features in SLE, and we investigated their roles as biomarkers.MethodsPeripheral blood cells obtained from 67 patients with SLE patients, 20 patients with rheumatoid arthritis (RA) and 23 healthy donors were subjected to real-time PCR in order to measure the transcriptional levels of seven interferon-inducible chemokines (RANTES, MCP-1, CCL19, MIG, IP-10, CXCL11, and IL-8). The data were used to calculate a chemokine score for each participant, after which comparisons were performed between various groups of SLE patients and control individuals.ResultsChemokine scores were significantly elevated in SLE patients versus RA patients and healthy donors (P = 0.012 and P = 0.002, respectively). Chemokine scores were correlated positively with SLE Disease Activity Index 2000 scores (P = 0.005) and negatively with C3 levels (P < 0.001). Compared with patients without lupus nephritis and those with inactive lupus nephritis, chemokine scores were elevated in patients with active lupus nephritis, especially when their daily prednisone dosage was under 30 mg (P = 0.002 and P = 0.014, respectively). Elevated chemokine scores were also associated with the presence of cumulative organ damage (Systemic Lupus International Collaborating Clinics/American Society of Rheumatology Damage Index ≥ 1; P = 0.010) and the occurrence of anti-Sm or anti-RNP autoantibodies (both P = 0.021).ConclusionsThe combined transcription level of interferon-inducible chemokines in peripheral blood leucocytes is closely associated with disease activity, degree of organ damage, and specific autoantibody patterns in SLE. The chemokine score may serve as a new biomarker for active and severe disease in SLE.
Highlights
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; there is increasing interest in identifying biomarkers for SLE
Peripheral blood cells obtained from 67 patients with SLE patients, 20 patients with rheumatoid arthritis (RA) and 23 healthy donors were subjected to real-time PCR in order to measure the transcriptional levels of seven interferon-inducible chemokines (RANTES, monocyte chemotactic protein (MCP)-1, CCL19, MIG, inducible protein 10 (IP-10), CXCL11, and IL-8)
The combined transcription level of interferoninducible chemokines in peripheral blood leucocytes is closely associated with disease activity, degree of organ damage, and specific autoantibody patterns in SLE
Summary
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; there is increasing interest in identifying biomarkers for SLE. We and others have used gene expression microarrays to identify a group of type I IFN-inducible genes (IFIGs) that are significantly upregulated in peripheral blood cells from SLE patients [1,2,3,4]. The expression of these IFIGs, often referred to as IFN signatures, was later found to be closely associated with increased disease activity, specific autoantibody profiles and significant organ damage in SLE patients [5,6]. Other functions of chemokines include their ability to influence dendritic cell maturation, induction of B-cell and T-cell development, determination of peripheral cell localization, and involvement in T-helper-1 and T-helper-2 polarization [8]
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