Methods for treating and diagnosing fibrotic and fibroproliferative diseases
The present invention provides compositions and methods for diagnosing and treating fibrotic lung disease.
1. A method of diagnosing a human subject with a fibrotic interstitial lung disease comprising determining the number of circulating fibrocytes in said subject, wherein an increase in the number of circulating fibrocytes in said subject compared to the number of circulating fibrocytes in a control subject is indicative of a fibrotic interstitial lung disease.
2. The method of claim 1 , wherein said fibrotic interstitial lung disease is selected from the group consisting of interstitial pneumonia, and non-specific interstitial pneumonia.
3. The method of claim 1 , wherein the number of circulating fibrocytes in said subject is at least about 10% greater, at least about 20% greater, at least about 30% greater, or at least about 50% greater than the number of circulating fibrocytes in said control subject.
4. The method of claim 1 , wherein the number of circulating fibrocytes in said subject is at least about 2 times greater or at least about 5 times greater than the number of circulating fibrocytes in said control subject.
5. The method of claim 1 , wherein said circulating fibrocytes are peripheral blood fibrocytes.
6. The method of claim 1 , wherein said circulating fibrocytes are collagen-1 expressing CD45+ cells.
7. The method of claim 1 or 6 , wherein said circulating fibrocytes are identified by flow cytometry.
8. The method of claim 1 , further comprising determining the percentage of circulating fibrocytes expressing α-SMA in said subject, wherein an increase in the percentage of circulating fibrocytes expressing α-SMA in said subject compared to the percentage of circulating fibrocytes expressing α-SMA in said control subject is indicative of a fibrotic lung disease or disorder.
9. The method of claim 8 , wherein said increase in expression of α-SMA is indicative of an increase in differentiation of said circulating fibrocytes into myofibroblasts.
10. The method of claim 1 , wherein said control subject is a subject that does not have a fibrotic lung disease or disorder.
11. A method of determining the progression of a fibrotic interstitial lung disease in a human subject suffering from a fibrotic intertitial lung disease comprising determining the number of circulating fibrocytes in said subject, wherein an increase over time in the number of circulating fibrocytes in said subject is indicative of a progression of said fibrotic interstitial lung disease or disorder.
12. The method of claim 11 , wherein said fibrotic interstitial disease is selected from the group consisting of interstitial pneumonia, and non-specific interstitial pneumonia.
13. The method of claim 11 , wherein said circulating fibrocytes are peripheral blood fibrocytes.
14. The method of claim 11 , wherein said circulating fibroblasts are collagen-1 expressing CD45+ cells.
15. The method of claim 11 or 14 , wherein said circulating fibroblasts are identified by flow cytometry.
16. The method of claim 11 , further comprising determining the percentage of circulating fibrocytes expressing α-SMA in said subject, wherein an increase in the percentage of circulating fibrocytes expressing α-SMA in said subject and an increase in the number of circulating fibrocytes in said subject is indicative of a progression of said fibotic interstitial lung disease.
17. The method of claim 16 , wherein said increase in expression of α-SMA is indicative of an increase in differentiation of said circulating fibrocytes into myofibroblasts.
18. The method of claim 11 , further comprising determining the amount of circulating CXCL-12 in said subject, wherein an increase in the amount of circulating CXCL-12 and an increase in the number of circulating fibrocytes in said subject is indicative of a progression of said fibrotic interstitial lung disease.
19. The method of claim 11 , further comprising comparing said number of circulating fibrocytes in the subject to the number of circulating fibrocytes in a control subject.
20. The method of claim 19 , wherein said control subject has a known stage of said fibrotic interstitial lung disease.