Follistatin-like protein-1 as a biomarker for inflammatory disorders

• US 8,741,584 B2
• Filed: 02/04/2013
• Issued: 06/03/2014
• Est. Priority Date: 08/05/2010
• 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, Wilson, David C.
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/758,405
• Publication Number:
  US 20130149712A1
• Time in Patent Office: 484 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: G01N 2800/102 Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
• CPC Class Codes: G01N 2800/328 Vasculitis, i.e. inflammation of blood vessels
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The present invention relates to methods and compositions for diagnosis of inflammatory disorders, and in non-limiting embodiments, of inflammatory disorders associated with elevated interleukin-1β (“IL-1β”), based on increased levels of follistatin-like protein 1 (“FSTL-1”). In particular non-limiting embodiments, the invention further provides for methods of identifying subjects with systemic onset juvenile idiopathic arthritis (“SOJIA”) who are at increased risk for developing macrophage activation syndrome (“MAS”) comprising detecting, in said subjects, hyper-increased levels of FSTL-1. In additional non-limiting embodiments, the invention provides for methods of identifying subjects with Kawasaki disease who are at increased risk of developing aortic aneurysms comprising detecting, in said subjects, hyper-increased levels of FSTL-1.

Claims

1. A method of diagnosing an inflammatory disorder in a human patient comprising:

(a) measuring the level of human FSTL-1 in a sample collected from the patient suspecting having an inflammatory disorder by an enzyme-linked immunosorbent assay; and

(b) diagnosing that the patient has an inflammatory disorder if the level of human FSTL-1 in the sample of the patient is measured to be between about 200 and 300 ng/ml, and

wherein the inflammatory disorder is systemic onset juvenile idiopathic arthritis or Kawasaki disease.

2. The method of claim 1, comprising comparing the level of human FSTL-1 measured in the sample of the patient to the level of human FSTL-1 measured in a sample of a healthy human control subject or an average level of human FSTL-1 measured in samples from a plurality of healthy human control subjects, where said level of human FSTL-1 in the sample of the control subject, or said average level of human FSTL-1 in the samples of the control subjects, is measured to be between about 125-160 ng/ml.

3. The method of claim 1, where the sample is a serum sample.

4. The method of claim 1, where the level of FSTL-1 is measured by a method that comprises reacting FSTL-1 in a subject sample with a capture ligand to bind FSTL-1 to the capture ligand, and then directly or indirectly detecting the presence of FSTL-1 bound to the capture ligand.

5. The method of claim 2, where the level of FSTL-1 is measured by a method that comprises reacting FSTL-1 in a subject sample with a capture ligand to bind FSTL-1 to the capture ligand, and then directly or indirectly detecting the presence of FSTL-1 bound to the capture ligand.

6. A method of identifying a patient with systemic onset juvenile idiopathic arthritis who is at increased risk for developing macrophage activation syndrome comprising:

(a) measuring the level of human FSTL-1 in a sample collected from the patient by an enzyme-linked immunosorbent assay; and

(b) identifying the patient with systemic onset juvenile idiopathic arthritis as being at increased risk for developing macrophage activation syndrome if the level of human FSTL-1 in the sample of the patient is measured to be increased by about 40 percent or more relative to control levels.

7. The method of claim 6, where the serum level of human FSTL-1 in the sample of the patient is measured to be about 230 ng/ml or greater.

8. The method of claim 6, where the level of FSTL-1 is measured by a method that comprises reacting FSTL-1 in a subject sample with a capture ligand to bind FSTL-1 to the capture ligand, and then directly or indirectly detecting the presence of FSTL-1 bound to the capture ligand.

9. A method of identifying a patient with Kawasaki disease who is at increased risk for developing macrophage activation syndrome comprising:

a) measuring the level of human FSTL-1 in a sample collected from the patient by an enzyme-linked immunosorbent assay; and

(b) identifying the patient with Kawasaki disease as being at increased risk for developing macrophage activation syndrome if the level of human FSTL-1 in the sample of the patient is measured to be increased by about 50 percent or more relative to control levels.

10. The method of claim 9, where the serum level of human FSTL-1 in the sample of the patient is measured to be about 200 ng/ml or greater.

11. The method of claim 9, where the level of FSTL-1 is measured by a method that comprises reacting FSTL-1 in a subject sample with a capture ligand to bind FSTL-1 to the capture ligand, and then directly or indirectly detecting the presence of FSTL-1 bound to the capture ligand.