INTERLEUKIN-33 (IL-33) FOR THE DIAGNOSIS AND PROGNOSIS OF CARDIOVASCULAR DISEASE

• US 20090305265A1
• Filed: 04/27/2007
• Published: 12/10/2009
• Est. Priority Date: 04/27/2006
• Status: Abandoned Application

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Jacobson, Sven, Snider, James V.
• Application Number:
  US12/298,613
• Publication Number:
  US 20090305265A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention includes methods for the use of interleukin-33 (IL-33) in the diagnosis of cardiovascular conditions including acute coronary syndrome (ACS), myocardial infarction, and/or heart failure, angina, cardiac hypertrophy, arteriosclerosis, myocarditis, pancarditis, endocarditis, stroke and/or pulmonary embolism and the determination of the severity of such conditions (prognosis).

Claims

1. A method of diagnosing a cardiovascular disease in a subject, the method comprising determining a level of IL-33 in a sample from a subject, wherein the level of IL-33 in the sample is indicative of whether the subject has a cardiovascular disease.

3. The method of claim 1, wherein determining a level of IL-33 in the sample comprises determining a level of one, two, or all three of mature IL-33, pre-IL-33, and pro-IL-33.

4. The method of claim 1, wherein the sample comprises blood, serum, plasma, urine, or body tissue.

5. The method of claim 1, further comprising comparing the level of IL-33 in the sample to a reference level, wherein the reference level represents a level in a subject who has or does not have cardiovascular disease.

7. The method of claim 1, wherein determining a level of IL-33 in the sample comprises contacting a binding composition to the sample, wherein the binding composition specifically binds to IL-33, and measuring or determining the specific binding of the binding composition to the sample.

8. The method of claim 7, wherein the binding composition comprises an antibody that binds specifically to IL-33 polypeptide.

9. The method of claim 8, wherein the binding composition comprises an oligonucleotide probes probe that bind binds specifically to IL-33 polynucleotide.

10. The method of claim 1, wherein the cardiac cardiovascular disease is acute coronary syndrome (ACS), myocardial infarction, heart failure, angina, cardiac hypertrophy, arteriosclerosis, myocarditis, pericarditis, endocarditis, stroke and/or or pulmonary embolism.

11. The method of claim 1, further comprising determining a level in the sample of one or more other biomarkers.

12. The method of claim 11, wherein the other biomarkers are selected from the group consisting of ST2, NT-proBNP, BNP, NT-proANP, and ANP, troponin, IMA, IL-6, CRP, creatinine, D-dimers, BUN, liver function enzymes, albumin, and bacterial endotoxin.

2. A method of determining the severity of a cardiovascular disease in a subject, the method comprising determining a level of IL-33 in a sample from a subject, wherein the level of IL-33 in the sample is indicative of the severity of the cardiovascular disease in the subject.

6. The method of claim 2, further comprising comparing the level of IL-33 in the sample to a reference level, wherein the reference level represents a level in a subject with a preselected severity of cardiovascular disease.

18. A kit for diagnosing cardiovascular disease, determining the severity of a cardiovascular disease, or monitoring cardiovascular disease in a subject, the kit comprising an antibody that specifically binds to IL-33, or an oligonucleotide probe that specifically binds to a nucleic acid encoding IL-33, and instructions for use in the method of claim 2.

19. A kit for diagnosing cardiovascular disease, determining the severity of a cardiovascular disease, or monitoring cardiovascular disease in a subject, the kit comprising an antibody that specifically binds to IL-33, or an oligonucleotide probe that specifically binds to a nucleic acid encoding IL-33, and instructions for use in the method of claim 2.

20. The method of claim 2, wherein determining a level of IL-33 in the sample comprises determining a level of one, two, or all three of mature IL-33, pre-IL-33, and pro-IL-33.

21. The method of claim 2, wherein the sample comprises blood, serum, plasma, urine, or body tissue.

22. The method of claim 2, wherein determining a level of IL-33 in the sample comprises contacting a binding composition to the sample, wherein the binding composition specifically binds to IL-33, and measuring or determining the specific binding of the binding composition to the sample.

23. The method of claim 22, wherein the binding composition is an antibody that binds specifically to IL-33 polypeptide.

24. The method of claim 23, wherein the binding composition is an oligonucleotide probes that bind specifically to IL-33 polynucleotide.

25. The method of claim 2, wherein the cardiac disease is acute coronary syndrome (ACS), myocardial infarction , heart failure, angina, cardiac hypertrophy, arteriosclerosis, myocarditis, pericarditis, endocarditis, stroke and/or pulmonary embolism.

26. The method of claim 2, further comprising determining a level in the sample of one or more other biomarkers.

27. The method of claim 26, wherein the other biomarkers are selected from the group consisting of ST2, NT-proBNP, BNP, NT-proANP, and ANP, troponin, MA, IL-6, CRP, creatinine, D-dimers, BUN, liver function enzymes, albumin, and bacterial endotoxin.

13. A method of monitoring the condition of a subject previously diagnosed with a cardiovascular condition, the method comprising:

determining a first level of IL-33 in a sample from a subject;

determining at least one subsequent level of IL-33 in a sample from the subject; and

comparing the level of IL-33 in the subsequent sample to the level of IL-33 in the first sample, wherein a difference in the IL-33 level in the subsequent sample relative to the level in the first sample is correlated with a change in the patient'"'"'s condition.

14. The method of claim 13, wherein the subject is undergoing treatment on an outpatient basis.

15. The method of claim 13, wherein an increase in IL-33 in the subsequent sample relative to the level in the first sample indicates that the patient'"'"'s condition is deteriorating.

16. The method of claim 15, wherein an increase in IL-33 in the subsequent sample relative to the level in the first sample indicates that the current treatment should be adjusted.

17. The method of claim 15, wherein an increase in IL-33 in the subsequent sample relative to the level in the first sample indicates that the patient should be admitted to a hospital for inpatient treatment.

28. A kit for diagnosing cardiovascular disease, determining the severity of a cardiovascular disease, or monitoring cardiovascular disease in a subject, the kit comprising an antibody that specifically binds to IL-33, or a oligonucleotide probe that specifically binds to a nucleic acid encoding IL-33, and instructions for use in the method of claim 13.