Diagnosis of sepsis or SIRS using biomarker profiles

• US 20040097460A1
• Filed: 11/12/2003
• Published: 05/20/2004
• Est. Priority Date: 11/12/2002
• Status: Abandoned Application

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Garrett, James, Tice, Gregory, Shi, Song, Moore, Richard L., Bachur, Nicholas Jr., Gentle, Thomas M. Jr., Rosenstein, Robert W., Goldenbaum, Paul E., Copertino, Donald, Ivey, Richard M., Towns, Michael L.
• Application Number:
  US10/704,661
• Publication Number:
  US 20040097460A1
• Time in Patent Office: Days
• US Class Current: 514/44.00R
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The early prediction or diagnosis of sepsis advantageously allows for clinical intervention before the disease rapidly progresses beyond initial stages to the more severe stages, such as severe sepsis or septic shock, which are associated with high mortality. Early prediction or diagnosis is accomplished using a molecular diagnostics approach, involving comparing an individual'"'"'s profile of biomarker expression to profiles obtained from one or more control, or reference, populations, which may include a population that develops sepsis. Recognition of features in the individual'"'"'s biomarker profile that are characteristic of the onset of sepsis allows a clinician to diagnose the onset of sepsis from a bodily fluid isolated at the individual at a single point in time. The necessity of monitoring the patient over a period of time is, therefore, avoided, advantageously allowing clinical intervention before the onset of serious symptoms of sepsis. Further, because the biomarker expression is assayed for its profile, identification of the particular biomarkers is unnecessary. The comparison of an individual'"'"'s biomarker profile to biomarker profiles of appropriate reference populations likewise can be used to diagnose SIRS in the individual.

Claims

1. A kit, comprising at least two nucleic acid host response biomarkers selected from the group of nucleic acids set forth in any one of TABLES 2-10 and their complements.

2. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 2 and their complements.

3. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 3 and their complements.

4. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 4 and their complements.

5. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 5 and their complements.

6. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 6 and their complements.

7. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 7 and their complements.

8. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 8 and their complements.

9. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 9 and their complements.

10. The kit of claim 1, wherein the at least two host response nucleic acid biomarkers are selected from the group of nucleic acids set forth in TABLE 10 and their complements.

11. A kit, comprising at least two oligonucleotide probes capable of hybridizing to at least two nucleic acid biomarkers selected from the group of nucleic acids set forth in any one of TABLES 2-10.

12. A biomarker profile, comprising at least two features that contribute to the prediction of the inclusion of an individual in a reference population with an accuracy of at least about 60%, wherein the features are measurable characteristics of a nucleic acid, and wherein the reference population is selected from the group consisting of a normal reference population, a SIRS-positive reference population, an infected/SIRS-negative reference population, a sepsis-positive reference population, a reference population at a stage in the progression of sepsis, a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 0-36 hours, a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 36-60 hours, and a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 60-84 hours.

13. A method of isolating a nucleic acid biomarker, comprising:

(a) obtaining a reference biomarker profile from a population of individuals;

(b) identifying a feature of said reference biomarker profile that is predictive or diagnostic of sepsis or one of the stages of sepsis, wherein the feature corresponds to a nucleic acid;

(c) identifying a nucleic acid biomarker that corresponds with said feature; and

(d) isolating said nucleic acid biomarker.