DNA sequences related to diagnosis and treatment of systemic inflammatory response syndrome
Inventors
Nie, Wensheng • Sweeney, Timothy
Assignees
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Publication Number
US-11104946-B2
Publication Date
2021-08-31
Expiration Date
Abstract
This invention provides triple primer and probe combinations that function efficiently in PCR-based amplification systems using undigested genomic DNA and are useful for the diagnosis and subsequent treatment of systemic inflammatory disease.
Core Innovation
The invention concerns treating systemic inflammatory response syndrome (SIRS) by selecting a patient presenting clinical symptoms of SIRS and having a biomarker gene score exceeding a threshold value indicating the presence of a bacterial or a viral infection. The biomarker gene score is based on measured expression levels in blood of at least two biomarker genes selected from IFI27, GPAA1, HK3, TNIP1, and LAX1.
The measured expression levels arise from amplification and detection of an mRNA subsequence encoding the biomarker genes, using amplification primer pairs in the presence of undigested genomic DNA and fluorescent probes that bind to the amplified biomarker gene subsequences. The primer pairs and probes are selected from defined primer and probe triplet member combinations, including variants defined by one nucleotide substitution relative to listed SEQ ID NOS and a GC content constraint.
The invention further includes diagnosing a bacterial or viral infection in a patient with SIRS by selecting a blood sample and quantitatively determining a diagnostic score indicative of bacterial or viral infection from measured levels of at least two biomarker genes selected from IFI27, GPAA1, HK3, TNIP1, and LAX1. The diagnostic score exceeds a threshold value generated by quantitative comparison of biomarker gene expression level scores from at least 100 patients known to have SIRS with bacterial or viral infection and 100 healthy controls.
Claims Coverage
The document provides three independent claims. Each independent claim centers on treating SIRS based on a biomarker gene score, a genetic amplification system that outputs a bacterial/viral likelihood score, and diagnosing bacterial or viral infection in SIRS using a score exceeding a threshold derived from patient and control comparisons.
Treating sirs based on a bacterial/viral biomarker gene score
A method of treating systemic inflammatory response syndrome (SIRS) by selecting a patient with SIRS symptoms and a biomarker gene score exceeding a threshold indicating bacterial or viral infection, where the biomarker gene score is based on measured expression levels in blood of at least two biomarker genes selected from IFI27, GPAA1, HK3, TNIP1, and LAX1, determined by amplification and detection of an mRNA subsequence encoding the biomarker genes using amplification primer pairs in the presence of undigested genomic DNA and fluorescent probes.
Genetic amplification system producing a bacterial/viral likelihood score
A genetic amplification system for diagnosing SIRS that measures expression levels of at least two biomarker genes by amplification and detection of a subsequence of mRNA encoding the biomarker genes and generates a score indicative of a likelihood of bacterial or viral infection, with reaction vessels comprising primer pairs and fluorescent probes binding to the amplified mRNA subsequences, using defined primer/probe triplet member combinations and allowed variants defined by nucleotide substitution and GC content.
Diagnosing bacterial/viral infection using a threshold derived from patient and healthy controls
A method of diagnosing a bacterial or viral infection in a patient with SIRS by selecting a blood sample and quantitatively determining a diagnostic score indicative of bacterial or viral infection based on measured levels of at least two biomarker genes selected from IFI27, GPAA1, HK3, TNIP1, and LAX1, where the diagnostic score exceeds a threshold value generated by quantitative comparison of biomarker gene expression level scores of at least 100 SIRS patients with bacterial or viral infection and 100 healthy controls.
Across the independent claims, the inventive approach is anchored in measuring blood mRNA subsequence expression of at least two biomarker genes using amplification and fluorescent probes, with defined primer/probe triplet combinations, to generate a biomarker gene score or diagnostic score used for bacterial versus viral indication in SIRS.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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