Treating or inhibiting severe sepsis based on measuring defensin alpha 4 (DEFA4) expression
Inventors
Brandon, Richard Bruce • MCHUGH, Leo Charles
Assignees
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Publication Number
US-12006548-B2
Publication Date
2024-06-11
Expiration Date
Abstract
Disclosed is a method for treating or inhibiting the development of severe sepsis in a subject based on measuring the level of a defensin alpha 4 (DEFA4) polynucleotide expression product.
Core Innovation
The invention relates to a method for treating or inhibiting the development of severe sepsis in a subject by using a peripheral blood biomarker profile. The method includes determining the biomarker profile for the subject by measuring the level of a defensin alpha 4 (DEFA4) polynucleotide expression product in the peripheral blood sample.
A sample biomarker profile is compared to a reference biomarker profile that correlates presence or absence of severe sepsis specifically with a reference level of the DEFA4 polynucleotide expression product. The comparing step includes comparing the level of the DEFA4 polynucleotide expression product in the sample biomarker profile to the level of the DEFA4 polynucleotide expression product in the reference biomarker profile.
Based on the comparison, the method determines whether the subject has an increased likelihood of the presence of severe sepsis. If the subject is determined to have an increased likelihood of the presence of severe sepsis, the method administers a therapy for treating severe sepsis.
Claims Coverage
The claim set includes one independent claim that defines a biomarker-guided treatment decision for severe sepsis using DEFA4 polynucleotide expression in peripheral blood, followed by therapy administration. Dependent claims add additional polynucleotide expression product correlation from a specified gene set, specify therapy options, and include adjunctive or palliative interventions.
Peripheral blood DEFA4 polynucleotide expression biomarker profiling
Determining a biomarker profile for a peripheral blood sample by measuring the level of a defensin alpha 4 (DEFA4) polynucleotide expression product in the peripheral blood sample.
Reference DEFA4-based severe sepsis correlation and comparison
Comparing the sample biomarker profile to a reference biomarker profile that correlates presence or absence of severe sepsis specifically with a reference level of the DEFA4 polynucleotide expression product, wherein the level of the DEFA4 polynucleotide expression product in the sample biomarker profile is compared to the level of the DEFA4 polynucleotide expression product in the reference biomarker profile.
Increased likelihood determination for severe sepsis
Determining whether the subject has an increased likelihood of the presence of severe sepsis based on the comparison of the sample biomarker profile to the reference biomarker profile.
Therapy administration when increased likelihood is present
Administering to the subject a therapy for treating severe sepsis if the subject is determined to have an increased likelihood of the presence of severe sepsis.
Selected therapy from an enumerated therapeutic set
Administering the therapy as a selection from a listed set of therapeutic agents, including antibiotics, anti-inflammatory/anti-pyretic agents, anti-tumor necrosis factor agents, recombinant protein C, oxygen support, vasoactive compounds, corticosteroids, an antibody to endotoxin, and therapies aimed at restoring or protecting organ function.
Additional polynucleotide expression product from a specified gene set for correlation
Correlating a reference biomarker profile with presence or absence of severe sepsis using a reference level of another polynucleotide expression product, measuring that other polynucleotide expression product in the sample, comparing the sample level to the reference biomarker profile level, and determining increased likelihood, where the other polynucleotide expression product is an expression product of a specified gene set.
Adjunctive or palliative therapy to modify oxygen, blood flow, or inflammation
Administering adjunctive or palliative therapy to a subject with an increased likelihood of the presence of severe sepsis to increase oxygen supply to major organs, increase blood flow to major organs, or reduce the inflammatory response.
Adjunctive or palliative therapy selected from non-steroidal anti-inflammatory drugs, intravenous fluids, and oxygen
Selecting the adjunctive or palliative therapy from non-steroidal anti-inflammatory drugs, intravenous fluids, and oxygen.
Overall, the claims cover a peripheral-blood DEFA4 biomarker determination with reference profile comparison to identify an increased likelihood of severe sepsis, followed by administering a severe-sepsis therapy. Dependent claims further specify therapy selection from enumerated agents, expand biomarker profiling by including an additional polynucleotide expression product from a specified gene set, and add adjunctive or palliative interventions aimed at oxygen supply, blood flow, and inflammation reduction, optionally limited to non-steroidal anti-inflammatory drugs, intravenous fluids, and oxygen.
Stated Advantages
Enables treating or inhibiting the development of severe sepsis by using a biomarker profile to determine increased likelihood and guide therapy administration.
Documented Applications
Distinguishing inSIRS versus ipSIRS using microarray data within a staged biomarker discovery and clinical assessment framework for SIRS/inSIRS/ipSIRS including severe sepsis stages.
Likelihood assessment of severe sepsis presence or absence in a subject based on comparing a sample biomarker profile to a reference biomarker profile.
Monitoring treatment response using refined signature biomarker sets for likelihood assessment.
Diagnosing or stratifying SIRS/inSIRS/ipSIRS and ipSIRS stages, including mild sepsis, severe sepsis, and septic shock.
Predicting the likelihood of SIRS/inSIRS/ipSIRS and ipSIRS stage occurrence.
Supporting monitoring of severity and treatment response.
Supporting triage and monitoring using example biomarker sets and statistical performance metrics (p-values/AUC) across disease stages/groups.
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