Biomarkers for a systemic lupus erythematosus (SLE) disease activity immune index that characterizes disease activity
Inventors
MUNROE, Melissa • JAMES, Judith • Jupe, Eldon • Purushothaman, Mohan
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Assignees
Member
Oklahoma Medical Research FoundationFounded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Founded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Publication Number
US-12510539-B2
Publication Date
2025-12-30
Expiration Date
Abstract
A method for characterizing disease activity in a systemic lupus erythematosus patient (SLE), comprising obtaining a dataset associated with a blood, serum, plasma or urine sample from the patient, assessing the dataset for a presence or an amount of protein expression of at least one innate serum or plasma mediator, assessing the dataset for a presence or an amount of protein expression of at least one adaptive serum or plasma mediator biomarker, assessing the dataset for a presence or an amount of at least one chemokine/adhesion molecule biomarker, assessing the dataset for a presence or an amount of at least one soluble TNF superfamily biomarker, assessing the dataset for a presence or an amount of at least one inflammatory mediator biomarker, assessing the dataset for a presence or an amount at least one SLE-associated autoantibody specificity biomarker and calculating a Lupus Disease Activity Immune Index (LDAII) score.
Core Innovation
The patent provides a method and validation data for calculating a Lupus Disease Activity Immune Index (LDAII) to characterize systemic lupus erythematosus (SLE) disease activity. The method obtains a dataset associated with a blood, serum, plasma or urine sample and measures panels of biomarkers across six categories: innate mediators, adaptive mediators, chemokines/adhesion molecules, soluble TNF superfamily members, inflammatory mediators, and SLE-associated autoantibodies. The LDAII is computed by log-transforming and standardizing mediator levels, weighting each mediator by its Spearman correlation to either number of autoantibody specificities or hSLEDAI, and summing the weighted values to produce an LDAII score.
The disclosure addresses characterizing disease activity in SLE patients to discriminate clinically active versus low disease and to relate immune mediator profiles to clinical indices and serologic burden. The LDAII variants (LDAII-33, LDAII-24, LDAII-12) are reported to discriminate active versus low disease, correlate with hSLEDAI and autoantibody burden, differentiate clinical and serologic subtypes and racial groups, and identify renal involvement using biomarkers including SCF, TNFRII, and MCP-1.
Claims Coverage
The patent includes two independent claims. The independent claims describe obtaining a patient sample dataset, measuring defined biomarker panels across six biomarker categories, calculating a Lupus Disease Activity Immune Index (LDAII), and administering treatment when the LDAII indicates prognosis for active disease.
Obtaining a patient sample dataset
Obtaining a dataset associated with a blood, serum, plasma or urine sample from the patient that comprises data representing the level of one or more biomarkers in the sample.
Innate mediator panel
Assessing the dataset for presence or amount of at least three innate serum or plasma mediator biomarkers selected from interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), interferon alpha (IFN-α), interleukin-15 (IL-15), interleukin-12 p70 (IL-12p70), interleukin-6 (IL-6), and interleukin-7 (IL-7).
Adaptive mediator panel
Assessing the dataset for presence or amount of at least three adaptive serum or plasma mediator biomarkers selected from interleukin-2 (IL-2), interleukin-2 receptor alpha chain (IL-2Rα), interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), interleukin-17A (IL-17A), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β).
Chemokine or adhesion molecule measurement
Assessing the dataset for presence or amount of at least one chemokine/adhesion molecule biomarker selected from interleukin-8 (IL-8), interferon gamma-induced protein (IP-10/CXCL10), monokine induced by gamma interferon (MIG/CXCL9), macrophage inflammatory protein-1 alpha (MIP-1α/CCL3), macrophage inflammatory protein-1 beta (MIP-1β/CCL4), macrophage chemoattractant protein-1 (MCP-1/CCL2), RANTES (CCL5), and MCP-3 (CCL7).
Soluble TNF superfamily measurement
Assessing the dataset for presence or amount of at least two soluble tumor necrosis factor (TNF) superfamily biomarkers selected from tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor 1 (TNFRI), tumor necrosis factor receptor 2 (TNFRII), Fas receptor (Fas), B lymphocyte stimulator (BLyS/BAFF), and TNF-related apoptosis-inducing ligand (TRAIL).
Inflammatory mediator measurement
Assessing the dataset for presence or amount of at least one inflammatory mediator biomarker selected from Osteopontin (OPN), Stem Cell Factor (SCF), and Resistin.
SLE-associated autoantibody panel
Assessing the dataset for presence or amount of multiple SLE-associated autoantibody specificity biomarkers selected from double-stranded DNA (dsDNA), chromatin, ribosomal P protein (RiboP), Ro/SSA, La/SSB, Sm protein (Sm), Ribonucleoprotein (RNP), and Sm/RNP (SmRNP), as specified by the claim minima.
Calculating an LDAII score
Calculating a Lupus Disease Activity Immune Index (LDAII) score from the measured biomarkers, wherein dependent claims specify log transformation, standardization, weighting by Spearman r correlation to autoantibody specificities or hSLEDAI in a second dataset, and summation of weighted marker values to yield the LDAII.
Performing an immunoassay to generate the dataset
Performing at least one immunoassay [procedural detail omitted for safety] on the patient sample to generate the dataset.
Administering treatment based on LDAII
Administering a treatment to the patient after determining, based on the LDAII score, that the patient has the prognosis for active disease, wherein the treatment comprises at least one of hydroxychloroquine (HCQ), belimumab, a nonsteroidal anti-inflammatory drug, or a steroid.
Independent claims 1 and 9 claim obtaining a patient sample dataset, measuring defined biomarker panels across six categories, calculating an LDAII score using specified data processing and weighting approaches, and administering specified treatments when the LDAII indicates active disease; claim 9 further requires performing at least one immunoassay and specifies minima for biomarkers measured.
Stated Advantages
LDAII variants (LDAII-33/24/12) discriminate active versus low disease.
LDAII correlates with hSLEDAI and autoantibody burden.
LDAII differentiates clinical and serologic subtypes and racial groups.
LDAII identifies renal involvement, notably via SCF, TNFRII, and MCP-1.
Documented Applications
Characterizing disease activity in a systemic lupus erythematosus patient using an LDAII score derived from biomarker measurements.
Evaluating disease activity and progression of SLE clinical disease by calculating an LDAII score from a patient sample dataset.
Guiding administration of treatment when the LDAII indicates prognosis for active disease, including hydroxychloroquine, belimumab, a nonsteroidal anti-inflammatory drug, or a steroid.
Classifying SLE severity into clinically active or quiescent and into serologically active (dsDNA binding and low complement) or serologically quiescent.
Identifying renal organ involvement by increased levels of SCF, TNFRII, and MCP-1.
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