Hepcidins as Biomarkers for Impending Lupus Nephritis Flare

• US 20100151487A1
• Filed: 05/19/2008
• Published: 06/17/2010
• Est. Priority Date: 05/21/2007
• Status: Active Grant

• Current Assignee: The Ohio State University Research Foundation
• Original Assignee: The Ohio State University Research Foundation
• Inventors: Zhang, Xiaolan, Rovin, Brad H.
• Granted Patent: US 8,313,950 B2
• Time in Patent Office: Days
• US Class Current: 435/7.100
• CPC Class Codes: G01N 2800/104 Lupus erythematosus [SLE]
• CPC Class Codes: G01N 2800/347 Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• 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 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

Biomarkers for determining a kidney flare episode in systemic lupus erythematosus are described.

Claims

1. A method for predicting a subject'"'"'s risk for a kidney flare episode, the method comprising detecting the status of one or more subject-derived hepcidin-20 and hepcidin-25 biomarkers in a sample taken from the subject.

2. A method of analyzing a subject sample for one or more subject-derived markers selected to identify at least a beginning of a kidney flare episode in a patient suffering from systemic lupus erythematosus (SLE), comprising:

assaying the sample for the presence or amount of one or more subject-derived hepcidin-20 and hepcidin-25 markers related to a kidney flare episode, and

characterizing the subject'"'"'s risk of having or the kidney flare episode disorders based upon the presence or amount of the hepcidin-20 and hepcidin-25 marker.

3. A method according to claim 2, wherein the method further comprises assaying the sample for the presence or amount of one or more subject-derived markers related to inflammation.

7. A method according to claim 2, wherein the characterization step is performed without comparing the amount of any of the hepcidin markers to a predetermined threshold amount, as determined for that subject.

8. A method according to claim 2, wherein the characterization step is performed without comparing the amount of any of the marker(s) related to inflammation to a predetermined threshold amount.

9. A method according to claim 2, wherein the subject sample is one or more of:

a urine sample, a serum sample, a plasma sample, and a blood sample.

10. A method according to claim 2, wherein the correlating step comprises comparing at least one hepcidin marker amount to a predetermined threshold level.

11. A test device for performing the method of claim 2, comprising:

a test surface comprising a plurality of discrete addressable locations corresponding to the subject-derived hepcidin markers, each the location comprising an antibody immobilized at the location selected to bind for detection one of the subject-derived hepcidin markers.

4. (canceled)

5. (canceled)

6. (canceled)

12. A method for assigning a therapy regimen and/or assigning a prognosis to a subject diagnosed with or suspected of suffering from systemic lupus erythematosus, comprising:

performing an assay method on a sample obtained from the subject, wherein the assay method provides one or more detectable signals related to the presence or amount of one or more subject-derived hepcidin-20 and hepcidin-25 markers; and

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

13. A method according to claim 12, wherein the method rules in or out an assignment of the subject to early goal-directed therapy.

14. A method according to claim 12, wherein the correlating step comprises comparing one or more subject-derived marker concentrations to a predetermined threshold level for a particular marker of interest.

15. A method according to claim 12, wherein the correlating step comprises:

determining the concentration of one or more subject-derived hepcidin-20 and hepcidin-25 markers,

calculating a single panel response value based on the concentration of the subject-derived hepcidin-20 and/or hepcidin-25 markers, and

comparing the panel response value to one or more predetermined threshold levels for the panel response value.

16. A method according to claim 12, wherein the correlating step comprises:

comparing one or more subject-derived hepcidin-20 and hepcidin-25 marker concentrations to a predetermined threshold level for a particular marker of interest and determining the concentration of the subject-derived hepcidin-20 and/or hepcidin-25 markers,

calculating a single panel response value based on the concentration of each of the subject-derived hepcidin-20 and/or hepcidin-25 markers, and

comparing the panel response value to a predetermined threshold level for the panel response value.

17. A method according to claim 12, wherein the markers comprise at least one marker related to inflammation, and at least one marker related to nephritis or one or more markers related thereto.

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

20. A method according to claim 12, wherein the sample is selected from the group consisting of blood, serum, urine, cerebrospinal fluid, and plasma.

21. A method according to claim 12, wherein the assay method comprises an immunoassay.

22. A method according to claim 12, wherein the assay method comprises mass spectrometry.

23. A method according to claim 12, wherein the method rules in or out one or more treatments for inclusion in a therapy regimen comprising administration of immunosuppressive therapy.

18. (canceled)

24. A diagnostic method, comprising:

determining a concentration of at least one of a hepcidin-20 or hepcidin-25 marker in a bodily fluid sample from a subject suffering from systemic lupus erythematosus,

wherein an increase in hepcidin-20 or hepcidin-25 concentration in the bodily fluid sample relative to a threshold hepcidin-20 or hepcidin-25 concentration indicates a kidney flare episode is likely to occur in the subject, and

wherein lack of an increase in hepcidin-20 or hepcidin-25 concentration in the bodily fluid sample relative to a threshold hepcidin-20 or hepcidin-25 concentration indicates a kidney flare episode is not likely to occur in the subject.

25. The method of claim 24, further comprising:

determining a concentration of hepcidin-20 in a bodily fluid sample from the subject,

wherein an increase in hepcidn-20 concentration in the bodily fluid sample relative to a threshold hepcidin-20 concentration indicates a kidney flare episode in the subject is likely to occur within about four months, and

wherein lack of an increase in hepcidin-20 concentration in the bodily fluid sample relative to a threshold hepcidin-20 concentration indicates a kidney flare episode is not likely to occur within about four months in the subject.

26. The method of claim 25, wherein the increase in hepcidin-20 is present at about four months prior to the presentation of symptoms of the kidney flare episode.

27. The method of claim 24, further comprising:

determining a concentration of hepcidin-25 in a bodily fluid sample from the subject,

wherein a decrease in hepcidn-25 concentration in the bodily fluid sample relative to a threshold hepcidin-25 concentration indicates a kidney flare episode in the subject, and

wherein lack of an decrease in hepcidin-25 concentration in the bodily fluid sample relative to a threshold hepcidin-25 concentration indicates a kidney flare episode is not present in the subject.

28. The method of claim 27, wherein the decrease in hepcidin-25 is present at about two months prior to the presentation of symptoms of the kidney flare episode.

29. A method for diagnosing a disease condition characterized by non-physiological levels of at least one of hepcidin-20 or hepcidin-25, comprising:

obtaining a tissue or fluid sample from a subject;

contacting the sample with an antibody or fragment thereof that specifically binds to one or more binding sites on hepcidin-20 and/or hepcidin-25, and

quantifying hepcidin-20 and/or hepcidin-25 level in the sample;

wherein the non-physiological level of hepcidin-20 and/or hepcidin-25 is indicative of the disease condition.

30. The method of claim 29, wherein the antibody specifically binds an epitope contained within amino acids 20 to 25 of hepcidin.

31. The method of claim 29, wherein the quantifying comprises conducting a SELDI-TOF-MS assay

32. A kit for detecting a disease condition characterized by non-physiological levels of one or more subject-derived hepcidin-20 and hepcidin-25 markers, comprising, an anti-hepcidin antibody or fragment thereof that specifically binds to one or more mid-portion or carboxy terminal epitopes of hepcidin, and a reagent that binds directly or indirectly to the antibody or fragment thereof.

33. The kit of claim 32, wherein the anti-hepcidin antibody or fragment thereof is immobilized on a support.

34. The kit of claim 32, wherein the reagent comprises hepcidin complexed with a first binding molecule.

35. A method of analyzing a subject sample for one or more subject-derived hepcidin-20 and hepcidin-25 markers selected to identify at least a beginning of a kidney flare episode in a patient suffering from systemic lupus erythematosus, comprising:

assaying the sample for the presence or amount of one or more subject-derived hepcidin-20 and hepcidin-25 markers related to a kidney flare-up episode,

wherein the markers comprise the up-regulation of hepcidin-20 at least as early as four months prior to onset of symptomatic indications of a kidney nephritis flare-up episode, and

wherein the down regulation of hepcidin-25 at least as early as two months prior to onset of symptomatic indications of a kidney nephritis flare-up episode, and

characterizing the subject'"'"'s risk of having or the kidney flare episode disorders based upon the presence or amount of the marker,

wherein the amount of at least one of the one or more subject-derived markers is not compared to a predetermined threshold amount.