Biomarkers for systemic lupus erythematosus disease activity, and intensity and flare
Inventors
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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-11585810-B2
Publication Date
2023-02-21
Expiration Date
Abstract
The present invention involves the identification of biomarkers that are predictive of impeding systemic lupus erythematosus (SLE) disease flare. Methods for treating patients so identified are also provided.
Core Innovation
The invention provides a method for assessing protein expression levels in a systemic lupus erythematosus (SLE) patient by obtaining a blood, serum, or plasma sample and assessing nine or more biomarkers across defined classes, including innate, Th1, Th2, and Th17 cytokines; chemokines and adhesion molecules; TNFR superfamily members; regulatory mediators; and SLE mediators such as SCF, IL-2Ra, and Resistin. A multianalyte soluble mediator signature is predictive of impending SLE flares.
The invention introduces a normalized, weighted Soluble Mediator Score that discriminates flare versus non-flare and correlates with SELENA-SLEDAI flare risk. The background identifies altered soluble mediator profiles that precede flares, with pro-inflammatory cytokines and shed TNF receptor family members elevated and regulatory mediators reduced, linking TNFR shedding to ADAM-family activity. The invention aims to provide a prognostic tool and to guide monitoring or targeted interventions [procedural detail omitted for safety].
Claims Coverage
This coverage identifies 8 inventive features across two independent claims.
Multianalyte biomarker panel of nine or more proteins
Obtaining a blood, serum, or plasma sample from an SLE patient and assessing expression levels of nine or more biomarkers in the sample.
Requirement of at least four chemokines or adhesion molecules
At least four chemokine(s) or adhesion molecules selected from CCL2/MCP-1, CCL3/MIP-1α, CXCL10/IP-10, CXCL9/MIG, CCL4/MIP-1β, ICAM-1, CCL7/MCP-3, VCAM-1, and CXCL8/IL-8.
Inclusion of at least two TNF receptor superfamily members
At least two TNFR superfamily member molecules selected from TNFRI, TNFRII, TRAIL, BLyS, Fas, NGF-β, and TNF-α.
Inclusion of at least two regulatory mediators
At least two regulatory mediator molecules selected from TGF-β, IL-1RA, and IL-10.
Inclusion of at least one SLE mediator (SCF, IL-2Ra, or Resistin)
At least one SLE mediator molecule selected from SCF, IL-2Ra, and Resistin.
Optional inclusion of cytokines from innate, Th1, Th2, and Th17 classes
Optionally includes one or more innate cytokines (IL-7, IL-1α, IL-1β), Th1 cytokines (IFN-γ, IL-12p70, IL-2, IL-2Rα), Th2 cytokines (IL-4, IL-13), and Th17 cytokines (IL-17A, IL-6, IL-21, IL-23).
Explicit inclusion of TGF-β and IL-10
An independent claim specifies the regulatory mediators TGF-β and IL-10 as required components of the assessed biomarkers.
Determination of increased or decreased expression relative to healthy subjects
For each of the nine or more biomarkers, determining whether the assessed expression level is decreased or increased relative to expression levels of each biomarker from a healthy subject.
The independent claims require assessing a multianalyte panel of nine or more protein biomarkers in a blood, serum, or plasma sample with defined class composition constraints, including at least four chemokines/adhesion molecules, at least two TNFR superfamily members, at least two regulatory mediators (with one claim specifying TGF-β and IL-10), at least one SLE mediator (SCF, Resistin, or IL-2Ra), optional cytokines from innate, Th1, Th2, and Th17 classes, and comparison to healthy-subject levels.
Stated Advantages
Provides a multianalyte soluble mediator signature that is predictive of impending SLE flares.
A normalized, weighted Soluble Mediator Score that discriminates flare versus non-flare and correlates with SELENA-SLEDAI flare risk.
Use of the biomarker panel and score for monitoring treatment efficacy.
Can guide monitoring or targeted interventions for SLE patients.
Documented Applications
Assessing protein expression levels in an SLE patient using a blood, serum, or plasma sample by measuring nine or more specified biomarkers.
Predicting impending systemic lupus erythematosus (SLE) flares using a multianalyte soluble mediator signature and Soluble Mediator Score.
Monitoring treatment efficacy in SLE patients using the biomarker panel and Soluble Mediator Score.
Guiding monitoring or targeted interventions for SLE patients based on the mediator profile or mediator score.
Kit compositions comprising bead-bound reagents for assessing the biomarker panel.
Use of measurement platforms [procedural detail omitted for safety] for assessing biomarkers.
Combined clinical operations alongside the biomarker assessment such as [procedural detail omitted for safety].
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