Biomarkers For A Systemic Lupus Erythematosus (SLE) Disease Activity Immune Index That Characterizes Disease Activity

A method of evaluating disease activity and progression of Systemic Lupus Erythematosus (SLE) clinical disease in a patient comprising:

• obtaining a blood, serum, plasma or urine sample from the patient;
• performing at least one immunoassay on the blood, serum, plasma or urine sample from the patient to generate a dataset comprising at least one biomarker from each of (1) to (6):
• (1) assessing the dataset for a presence or an amount of protein expression of at least one innate serum or plasma mediator biomarker selected from the group consisting of:
• interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-1RA (IL-1RA), interferon-α (IFN-α), interleukin-12p70 (IL-12p70), interleukin-6 (IL-6), and interleukin-23p19 (IL-23p19);
• (2) assessing the dataset for a presence or an amount of protein expression of at least one adaptive serum or plasma mediator biomarker selected from the group consisting of:
• interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-5 (IL-5), interleukin-13 (IL-13), interleukin-17A (IL-17A), interleukin-21 (IL-21), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β);
• (3) assessing the dataset for a presence or an amount of at least one chemokine/adhesion molecule biomarker selected from the group consisting of:
• interleukin-8 (IL-8) (chemokine (C—X—C motif) ligand 8 (CXCL8)), interferon gamma-induced protein (IP-10) (chemokine (C—X—C motif) ligand 10 (CXCL10)), monokine induced by gamma interferon (MIG) (chemokine (C—X—C motif) ligand 9 (CXCL9)), macrophage inflammatory protein-1α (MIP-1α) (chemokine (C—C motif) ligand 3 (CCL3)), macrophage inflammatory protein-1β (MIP-1β) (chemokine (C—C motif) ligand 4 (CCL4)), monocyte chemoattractant protein 1 (MCP-1) (chemokine (C—C motif) ligand 2 (CCL2)), monocyte chemoattractant protein 3 (MCP-3) (chemokine (C—C motif) ligand 7 (CCL7)), and Intercellular Adhesion Molecule 1 (ICAM-1);
• (4) assessing the dataset for a presence or an amount of at least one soluble TNF superfamily biomarker selected from the group consisting of:
• tumor necrosis factor receptor I (TNFRI), tumor necrosis factor receptor II (TNFRII)), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related weak inducer of apoptosis (TWEAK), CD40 ligand (CD40L) (cluster of differentiation 154 (CD154)), B lymphocyte stimulator (BLyS), and A proliferation-inducing ligand (APRIL);
• (5) assessing the dataset for a presence or an amount of the inflammatory mediator biomarker stem cell factor (SCF);
• and
• (6) assessing the dataset for a presence or an amount at least one SLE-associated autoantibody specificity biomarker selected from the group consisting of:
• double stranded DNA (dsDNA), chromatin, ribosomal P (RiboP), Sjögren's-syndrome-related antigen A (Ro/SSA), Sjögren's-syndrome-related antigen B (La/SSB), Smith (Sm), Smith ribonuclear protein (SmRNP), and ribonuclear protein (RNP);
• calculating a Lupus Disease Activity Immune Index (LDAII) score, and
• implementing SLE clinical management comprising one or both of monitoring of the SLE subject having classified SLE, administering a treatment to the SLE subject having classified SLE who has a likelihood of future SLE disease activity.

A method of calculating a Lupus Disease Activity Immune Index (LDAII) by measuring expression levels of a set of biomarkers in a subject comprising:

• determining biomarker measures of a set of biomarkers by immunoassay in a physiological sample, wherein the biomarkers are peptides, proteins, peptides bearing post-translational modifications, proteins bearing post-translational modification, or a combination thereof;
• wherein the physiological sample is whole blood, blood plasma, blood serum, or a combination thereof;
• wherein the set of biomarkers comprise a dataset of measurements selected from at least one of each category of biomarkers selected from:
• a presence or an amount of protein expression of at least one innate serum or plasma mediator biomarker dataset selected from:
• IL-1α, IL-1β, IL-1RA, IFN-α, IL-12p70, IL-6, and IL-23p19;
• a presence or an amount of protein expression of at least one adaptive serum or plasma mediator biomarker dataset selected from:
• IL-2, IFN-γ, IL-5, IL-13, IL-17A, IL-21, IL-10, and TGF-β;
• a presence or an amount of at least one chemokine/adhesion molecule biomarker dataset selected from:
• IL-8/CXCL8, IP-10/CXCL10, MIG/CXCL9, MIP-1α/CCL3, MIP-1β/CCL4, MCP-1/CCL2, MCP-3/CCL7, and ICAM-1;
• a presence or an amount of at least one soluble TNF superfamily biomarker dataset selected from:
• TNFRI, TNFRII, TRAIL, TWEAK, CD40L/CD154, BLyS, and APRIL;
• a presence or an amount of the inflammatory mediator biomarker SCF;
• and
• a presence or an amount at least one SLE-associated autoantibody specificity biomarker dataset selected from:
• dsDNA, chromatin, RiboP, Ro/SSA, La/SSB, Sm, SmRNP, and RNP;
• and
• calculating an LDAII score, whereby the dataset is:
• log transformed;
• standardized;
• weighted by Spearman r correlation to the autoantibody specificities in the second dataset, and a summation of the soluble protein markers equals an LDAII score.