Methods for diagnosis of sepsis

• US 10,533,224 B2
• Filed: 03/12/2016
• Issued: 01/14/2020
• Est. Priority Date: 03/12/2015
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Khatri, Purvesh, Sweeney, Timothy E.
• Primary Examiner(s): Dunston, Jennifer
• Application Number:
  US15/526,306
• Publication Number:
  US 20180291449A1
• Time in Patent Office: 1,403 Days
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 25/20 Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods for diagnosis of sepsis are disclosed. In particular, the invention relates to the use of biomarkers for aiding diagnosis, prognosis, and treatment of sepsis, and to a panel of biomarkers that can be used to distinguish sepsis from noninfectious sources of inflammation, such as caused by traumatic injury, surgery, autoimmune disease, thrombosis, or systemic inflammatory response syndrome (SIRS).

Claims

1. A method for treating a subject for sepsis, comprising:

(a) identifying a human subject as having increased levels of expression of CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, and C3AR1 biomarkers and decreased levels of expression of KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 biomarkers relative to a time-matched, control subject with non-infectious inflammation; and

(b) administering an antibiotic to the human subject.

2. The method of claim 1, wherein the antibiotic is a broad spectrum antibiotic.

3. The method of claim 1, wherein the levels of expression of the biomarkers are measured by microarray analysis, polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR), isothermal amplification, a Northern blot, or a serial analysis of gene expression (SAGE).

4. The method of claim 1, wherein the method comprises identifying the human subject as having increased levels of expression of the CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, and C3AR1 biomarkers and decreased levels of expression of the KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 biomarkers in whole blood, buffy coat, plasma, serum, peripheral blood mononucleated cells (PBMCS), band cells, neutrophils, monocytes, or T cells relative to a corresponding sample from the time matched control subject with non-infectious inflammation.

5. The method of claim 1, wherein the method further comprises:

receiving values indicating the levels of expression of the CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 biomarkers in a biological sample from the patient.

6. A method for treating a human subject for sepsis, comprising:

(a) calculating a sepsis score for the human subject based on individual expression levels of CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1;

(b) diagnosing the human subject as having sepsis based on the sepsis score; and

(c) administering an antibiotic to the diagnosed human subject.