Follistatin-like protein-1 as a biomarker for sepsis

• US 8,658,379 B2
• Filed: 06/29/2012
• Issued: 02/25/2014
• Est. Priority Date: 01/29/2008
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Hirsch, Raphael
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/538,918
• Publication Number:
  US 20130011863A1
• Time in Patent Office: 606 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2333/4703 Regulators; Modulating activity
• 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 present invention relates to methods and kits for diagnosing systemic inflammatory response syndrome or sepsis using levels of FSTL-1.

Claims

1. A method of diagnosing sepsis in a subject, comprising (i) determining the level of follistatin-like protein-1 in a serum sample from a subject manifesting one or more of:

an identified locus of infection, fever or a body temperature lower than normal;

tachycardia;

tachypnea;

an elevated white blood cell count or neutropenia and/or greater than 10% immature band forms;

(ii) comparing the level of follistatin-like protein-1 in the serum sample to a control level of follistatin-like protein-1 as determined by measuring the follistatin-like protein-1 level in serum from one or more healthy subjects, and (iii) diagnosing sepsis where a serum level of follistatin-like protein-1 in the sample of the subject is at least 50% higher than the control level of follistatin-like protein-1 indicates that the subject has sepsis.

3. The method of claim 1 or 2, where the level of follistatin-like protein-1 is determined by enzyme linked immunosorbent assay.

4. The method of claim 1, 2 or 3, where the human subject has been determined to not suffer from an autoimmune disease.

2. A method of diagnosing sepsis in a human subject, comprising (i) determining the level of follistatin-like protein-1 in a serum sample from a human subject manifesting one or more of:

an identified locus of infection, a body temperature greater than 38.3°

C. or less than 36°

C.;

a heart rate greater than 90 beats/min;

a respiratory rate greater than 20 breaths per minute and/or PaCO₂ less than 32 mm Hg;

a white blood cell count greater than 12×

10⁹ per liter or less than 4×

10⁹ per liter, and/or greater than 10% immature band forms;

(ii) comparing the level of follistatin-like protein-1 in the serum sample to a control level of follistatin-like protein-1 as determined by measuring the follistatin-like protein-1 level in serum from one or more healthy human subjects, and (iii) diagnosing sepsis where a serum level of follistatin-like protein-1 in the sample of the subject is at least 50% higher than the control level of follistatin-like protein-1 indicates that the subject has sepsis.

5. The method of claim 2, 3 or 4, where the human subject has not previously been diagnosed with autoimmune arthritis.

6. A method of diagnosing sepsis in a human subject, comprising (i) determining the level of follistatin-like protein-1 in a serum sample from a human subject manifesting one or more of:

an identified locus of infection, a body temperature greater than 38.3°

C. or less than 36°

C.;

a heart rate greater than 90 beats/min;

a respiratory rate greater than 20 breaths per minute and/or PaCO₂ less than 32 mm Hg;

a white blood cell count greater than 12×

10⁹ per liter or less than 4×

10⁹ per liter, and/or greater than 10% immature band forms; and

(ii) diagnosing sepsis where the serum level of the subject is above 120 ng/ml.

7. The method of claim 6, where the level of follistatin-like protein-1 is determined by enzyme linked immunosorbent assay.

8. The method of claim 6 or 7, where the human subject has been determined to not suffer from an autoimmune disease.

9. The method of claim 6, 7 or 8, where the human subject has not previously been diagnosed with autoimmune arthritis.

10. The method of claim 6, 7, 8 or 9 where the level of follistatin-like protein-1 in the serum sample is greater than 150 ng/ml.

11. The method of claim 6, 7, 8 or 9 where the level of follistatin-like protein-1 in the serum sample is greater than or equal to 200 ng/ml.