Biomarkers for Systemic Lupus Erythematosus Disease Activity, and Intensity and Flare

A method of diagnosing a systemic lupus erythematosus (SLE) patient as undergoing a pre-flare event, the method comprising:

• obtaining a blood, serum, or plasma sample from the SLE patient;
• assessing expression levels of 9 or more biomarkers in the sample from the SLE patient, wherein the biomarkers are selected from:
• innate cytokines selected from IL-7, IL-1α, and IL-1β;
• Th1 cytokines selected from interferon-gamma (IFN-γ), IL-12p70, IL-2, and IL-2Rα;
• Th2 cytokines selected from IL-4 and IL-13;
• Th17 cytokines selected from IL-17A, IL-6, IL-21, and IL-23;
• chemokine(s) or adhesion molecules selected from C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1 alpha (MIP-1α), C-X-C motif chemokine ligand 10 (CXCL10)/IFN-gamma-inducible protein 10 (IP-10), C-X-C motif chemokine ligand 9 (CXCL9)/monokine induced by interferon-gamma (MIG), C-C motif chemokine ligand 4 (CCL4)/macrophage inflammatory protein-1 beta (MIP-1(3), Intercellular Adhesion Molecule 1 (ICAM-1), CCL7/MCP-3, VCAM-1, and CXCL8/IL-8;
• TNFR superfamily member molecules selected from tumor necrosis factor receptor I (TNFRI), tumor necrosis factor receptor II (TNFRII), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas, NGF-β, and TNF-α;
• regulatory mediator molecules selected from native transforming growth factor beta (native TGF-β), an interleukin-1 receptor antagonist (IL-1RA), a total transforming growth factor beta (total TGF-β), and IL-10;
• and
• SLE mediator molecules selected from a stem cell factor (SCF) and Resistin.

A kit comprising:

• a set of reagents for determining expression levels of 9 or more biomarkers in a sample from a SLE patient, wherein the biomarkers are selected from:
• innate cytokines selected from IL-7, IL-1α, and IL-1β;
• Th1 cytokines selected from interferon-gamma (IFN-γ), IL-12p70, IL-2, and IL-2Rα;
• Th2 cytokines selected from IL-4 and IL-13;
• Th17 cytokines selected from IL-17A, IL-6, IL-21, and IL-23;
• chemokine(s) or adhesion molecules selected from C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1 alpha (MIP-1α), C-X-C motif chemokine ligand 10 (CXCL10)/IFN-gamma-inducible protein 10 (IP-10), C-X-C motif chemokine ligand 9 (CXCL9)/monokine induced by interferon-gamma (MIG), C-C motif chemokine ligand 4 (CCL4)/macrophage inflammatory protein-1 beta (MIP-13), Intercellular Adhesion Molecule 1 (ICAM-1), CCL7/MCP-3, VCAM-1, and CXCL8/IL-8;
• TNFR superfamily member molecules selected from tumor necrosis factor receptor I (TNFRI), tumor necrosis factor receptor II (TNFRII), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas, NGF-β, and TNF-α;
• regulatory mediator molecules selected from native transforming growth factor beta (native TGF-β), an interleukin-1 receptor antagonist (IL-1RA), a total transforming growth factor beta (total TGF-β), and IL-10;
• and
• SLE mediator molecules selected from a stem cell factor (SCF) and Resistin;
• and
• instructions for using the set of reagents to determine the expression levels of biomarkers from the test sample.

A method of diagnosing a systemic lupus erythematosus (SLE) patient as undergoing a pre-flare event, the method comprising:

• obtaining a blood, serum, or plasma sample from the SLE patient;
• assessing expression levels of 9 or more biomarkers in the sample from the SLE patient, wherein the biomarkers are selected from:
• at least four chemokine(s) or adhesion molecules selected from C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1 alpha (MIP-1α), C-X-C motif chemokine ligand 10 (CXCL10)/IFN-gamma-inducible protein 10 (IP-10), C-X-C motif chemokine ligand 9 (CXCL9)/monokine induced by interferon-gamma (MIG), C-C motif chemokine ligand 4 (CCL4)/macrophage inflammatory protein-1 beta (MIP-1(3), Intercellular Adhesion Molecule 1 (ICAM-1), CCL7/MCP-3, VCAM-1, and CXCL8/IL-8;
• at least two TNFR superfamily member molecules selected from tumor necrosis factor receptor I (TNFRI), tumor necrosis factor receptor II (TNFRII), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas, NGF-β, and TNF-α;
• at least one regulatory mediator molecule selected from transforming growth factor beta (TGF-β) and IL-10;
• and
• at least one SLE mediator molecule selected from a stem cell factor (SCF), IL-2RA, and Resistin;
• and
• diagnosing the pre-flare event in the SLE patient based on the expression levels of the 9 or more biomarkers.