Methods and compositions for determining treatment regimens in systemic inflammatory response syndromes

• US 20050148029A1
• Filed: 12/23/2004
• Published: 07/07/2005
• Est. Priority Date: 09/29/2003
• Status: Abandoned Application

• Current Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Original Assignee: BIOSITE INCORPORATED (Abbott Laboratories Incorporated)
• Inventors: Buechler, Kenneth F., McPherson, Paul H., Anderberg, Joseph Michael
• Application Number:
  US11/022,552
• Publication Number:
  US 20050148029A1
• Time in Patent Office: Days
• US Class Current: 435/7.100
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/525 Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 2333/54 Interleukins [IL]
• CPC Class Codes: G01N 2333/58 Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
• CPC Class Codes: G01N 2333/585 Calcitonins
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The present invention relates to methods and compositions for symptom-based differential diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to methods and compositions selected to rule in or out SIRS, or for differentiating sepsis, severe sepsis, septic shock and/or MODS from each other and/or from non-infectious SIRS.

Claims

1. A method for assigning a therapy regimen and/or assigning a prognosis to a subject diagnosed with or suspected of suffering from SIRS, sepsis, severe sepsis, septic shock, or MODS, comprising:

performing an assay method on a sample obtained from said subject, wherein said assay method provides one or more detectable signals related to the presence or amount of one or more subject-derived markers independently selected from the group consisting of markers related to blood pressure regulation, markers related to inflammation, markers related to apoptosis, and markers related to coagulation and hemostasis, or markers related to said subject-derived markers, optionally further comprising one or more detectable signals related to the presence or amount of one or more subject-derived markers of tissue injury; and

correlating the signal(s) obtained from said assay method to ruling in or out a therapy regimen for said subject and/or assigning a prognosis to said subject.

2. A method according to claim 1, wherein the method rules in or out an assignment of said subject to early goal-directed therapy.

3. A method according to claim 1, wherein the correlating step comprises comparing one or more subject-derived marker concentrations to a predetermined threshold level for a particular marker of interest.

4. A method according to claim 1, wherein the correlating step comprises determining the concentration of each of a plurality of subject-derived markers, calculating a single panel response value based on the concentration of each of said plurality of subject-derived markers, and comparing the panel response value to one or more predetermined threshold levels for said panel response value.

5. A method according to claim 1, wherein the correlating step comprises comparing one or more subject-derived marker concentrations to a predetermined threshold level for a particular marker of interest and determining the concentration of each of a plurality of subject-derived markers, calculating a single panel response value based on the concentration of each of said plurality of subject-derived markers, and comparing the panel response value to a predetermined threshold level for said panel response value.

6. A method according to claim 1, wherein said one or more subject-derived markers comprise at least one marker selected from the group consisting of matrix metalloproteinase 9 (MMP-9), interleukin-1β

(IL-1β

), interleukin-6 (IL-6), interleukin-8 (IL-8), IL-8_6-77, interleukin-10 (IL-10), interleukin-22 (IL-22), IL-1 receptor agonist (IL-1ra), CXCL6, CXCL13, CXCL16, CCL8, CCL20, CCL23, CCL26, D-dimer, HMG-1, tumor necrosis factor-α

(TNF-α

), B-type natriuretic protein (BNP), A-type natriuretic protein (ANP), C-type natriuretic protein (BNP), C-reactive protein (CRP), caspase-3, calcitonin, procalcitonin_3-116, soluble DPP-IV, soluble FAS ligand (sFasL), creatine kinase-BB (CK-BB), vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1), or one or more markers related to said subject-derived markers.

7. A method according to claim 6, wherein said one or more subject-derived markers comprise at least one marker related to BNP selected from the group consisting of NT-proBNP, proBNP, BNP_79-108, and BNP_3-108.

8. A method according to claim 1, wherein the correlating step comprises determining the concentration of each of a plurality of subject-derived markers, wherein the plurality of markers comprise at least one interleukin or one or more markers related thereto.

9. A method according to claim 1, wherein the plurality of markers comprise at least one marker related to inflammation, and at least one marker related to coagulation and hemostasis or one or more markers related thereto.

10. A method according to claim 1, wherein the plurality of markers comprise at least one marker related to inflammation, and at least one marker related to blood pressure regulation, or one or more markers related thereto.

11. A method according to claim 1, wherein the plurality of markers comprise at least one marker related to blood pressure regulation, at least one marker related to inflammation, and at least one marker related to coagulation and hemostasis, or one or more markers related thereto.

12. A method according to claim 1, wherein the sample is from a human.

13. A method according to claim 1, wherein the sample is selected from the group consisting of blood, serum, urine, cerebrospinal fluid, and plasma.

14. A method according to claim 1, wherein the assay method comprises an immunoassay.

15. A method according to claim 1, wherein the assay method comprises mass spectrometry.

16. A method according to claim 1, wherein said one or more subject-derived markers comprise one or more markers related to blood pressure regulation selected from the group consisting of ANP, BNP, a marker related to BNP, CNP, urotensin II, arginine vasopressin, aldosterone, angiotensin I, angiotensin II, angiotensin III, bradykinin, calcitonin, procalcitonin, calcitonin gene related peptide, adrenomedullin, calcyphosine, endothelin-2, endothelin-3, renin, and urodilatin, or one or more markers related thereto.

17. A method according to claim 1, wherein said one or more subject-derived markers comprise one or more markers related to inflammation selected from the group consisting of acute phase reactants, vascular cell adhesion molecule, intercellular adhesion molecule-1, intercellular adhesion molecule-2, intercellular adhesion molecule-3, CRP, HMG-1, IL-1β

, IL-6, IL-8, IL-8_6-77, IL-1ra, MCP-1;

caspase-3, lipocalin-type prostaglandin D synthase, mast cell tryptase, eosinophil cationic protein, KL-6, haptoglobin, TNF-α

, TNF-β

, TREM-1, fibronectin, macrophage migration inhibitory factor, and VEGF, or one or more markers related thereto.

18. A method according to claim 17, wherein said one or more subject-derived markers comprise one or more acute phase reactants selected from the group consisting of hepcidin, HSP-60, HSP-65, HSP-70, sFasL, asymmetric dimethylarginine, matrix metalloproteins 11, 3, and 9, defensin HBD 1, defensin HBD 2, serum amyloid A, oxidized LDL, insulin like growth factor, TNF-β

, an inter-α

-inhibitor, e-selectin, glutathione-S-transferase, hypoxia-inducible factor-1α

, inducible nitric oxide synthase, intracellular adhesion molecule, lactate dehydrogenase, monocyte chemoattractant peptide-1, n-acetyl aspartate, prostaglandin E2, receptor activator of nuclear factor ligand, TNF receptor superfamily member 1A, and cystatin C, or one or more markers related thereto.

19. A method according to claim 1, wherein said one or more subject-derived markers comprise one or more markers related to coagulation and hemostasis selected from the group consisting of plasmin, fibrinogen, D-dimer, β

-thromboglobulin, platelet factor 4, fibrinopeptide A, platelet-derived growth factor, prothrombin fragment 1+2, plasmin-α

2-antiplasmin complex, thrombin-antithrombin III complex, P-selectin, thrombin, von Willebrand factor, tissue factor, and thrombus precursor protein, or one or more markers related thereto.

20. A method according to claim 1, wherein said one or more subject-derived markers comprise one or more markers selected from the group consisting of CRP, HMG-1, caspase-3, creatine kinase-BB, MMP-9, IL-1β

, IL-1ra, IL-6, IL-8, TNFα

, MIF, MCP-1, BNP, CNP, pro-BNP, pro-CNP, NT-pro-BNP, tissue factor, von Willebrand factor, vWF-A1, vWF-integrin binding domain, and vWF-A3, or one or more markers related thereto.

21. A method according to claim 1, wherein said one or more subject-derived markers comprise BNP or a marker related to BNP.

22. A method according to claim 21, wherein said one or more subject-derived markers further comprise one or more markers selected from the group consisting of CRP, HMG-1, HSP-60, IL-1ra, MMP-9, an interleukin, CK-BB, sICAM-1, caspase-3, tissue factor, TNF-α

, sFasL, MPO, VEGF, D-dimer, and MCP-1, or one or more markers related thereto.

23. A method according to claim 1, wherein the method rules in or out one or more treatments for inclusion in a therapy regimen selected from the group consisting of administration of intravenous antibiotic therapy, maintenance of a central venous pressure of 8-12 mm Hg, administration of crystalloids and/or colloids, maintenance of a mean arterial pressure of ≧

65 mm Hg, administration of one or more vasopressors, administration of one or more vasodilators, administration of one or more corticosteroids, administration of recombinant activated protein C, maintenance of a central venous oxygen saturation of ≧

70%, administration of transfused red blood cells to a hematocrit of at least 30%, administration of one or more inotropics, and administration of mechanical ventilation.