Biomarkers for Systemic Lupus Erythematosus Disease Activity, and Intensity and Flare

Abstract

The present invention involves the identification of biomarkers that are predictive of impeding systemic lupus erythematosus (SLE) disease flare. Methods for treating patients so identified are also provided.

1 . A method of diagnosing a systemtic lupus erythematosus (SLE) patient as undergoing a pre-flare event comprising:
 (a) obtaining a blood, serum or plasma sample from a patient;   (b) assessing the level of at least one of each of the following:
 (i) innate type cytokine, (ii) Th1 type cytokine, (iii) Th2 type cytokine, and (iv) Th17 type cytokine, 
   plus at least two each of the following:
 (i) a chemokines/adhesion molecule, (ii) a TNFR superfamily member, (iii) a regulatory mediator and (iv) other SLE mediator; 
   and   (c) diagnosing said patient as undergoing a pre-flare event when the majority of innate, Th1, Th2, Th17 type cytokines, chemokines/adhesion molecules, TNFR superfamily members and other mediators are elevated, and at least two regulatory mediators are reduced, as compared to an SLE patient not undergoing a pre-flare event.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein assessing comprises immunologic detection. 
     
     
         6 . The method of  claim 5 , wherein immunologic detection comprises flow cytometry, ELISA, RIA or Western blot. 
     
     
         7 . The method of  claim 5 , wherein immunologic detection comprises a multiplexed bead-based assay. 
     
     
         8 . The method of  claim 1 , wherein assessing comprises detection of transcripts. 
     
     
         9 . The method of  claim 8 , wherein detection transcripts comprises amplification of mRNA. 
     
     
         10 . The method of  claim 9 , wherein said amplification comprises RT-PCR. 
     
     
         11 . The method of  claim 1 , further comprising performing one or more of a SLEDA Index analysis on said patient, anti-nuclear antibody (ANA) testing in a sample from said patient and/or anti-extractable nuclear antigen (anti-ENA) in a sample from said patient. 
     
     
         12 . The method of  claim 1 , further comprising taking a medical history of said patient. 
     
     
         13 . The method of  claim 1 , further comprising treating said patient. 
     
     
         14 . The method of  claim 1 , wherein said SLE patient not undergoing a flare event is represented by a sample from the same patient during a non-flare period. 
     
     
         15 . The method of  claim 1 , wherein said SLE patient not undergoing a flare is represented by a pre-determined average level. 
     
     
         16 . A method of assessing the efficacy of a treatment for systemic lupus erythematosus (SLE) in a patient comprising:
 (a) obtaining a blood, serum or plasma sample from a patient; and   (b) assessing the level of at least one of each of the following:
 (i) innate type cytokine, (ii) Th1 type cytokine, (iii) Th2 type cytokine, and (iv) Th17 type cytokine, 
   plus at least two each of the following:
 (i) a chemokines/adhesion molecule, (ii) a TNFR superfamily member, (iii) a regulatory mediator and (iv) other SLE mediator; 
   and   (c) when the majority of innate, Th1, Th2, Th17 type cytokines, chemokines/adhesion molecules, TNFR superfamily members and other SLE mediators are reduced, and at least two regulatory mediators are elevated, as compared to a level in a previous sample from said SLE patient.   
     
     
         17 - 19 . (canceled) 
     
     
         20 . The method of  claim 16 , wherein assessing comprises immunologic detection. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of  claim 16 , wherein assessing comprises detection of transcripts. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The method of  claim 16 , further comprising performing one or more of a SLEDA Index analysis on said patient, anti-nuclear antibody (ANA) testing in a sample from said patient and/or anti-extractable nuclear antigen (anti-ENA) in a sample from said patient. 
     
     
         27 . The method of  claim 16 , further comprising taking a medical history of said patient and/or treating said patient. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 16 , wherein said SLE patient not undergoing a flare event is represented by a sample from the same patient during a non-flare period. 
     
     
         30 . The method of  claim 16 , wherein said SLE patient not undergoing a flare is represented by a pre-determined average level. 
     
     
         31 . A kit comprising:
 (a) one or more reagents for assessing the expression of biomarkers including at least one innate cytokine, a least one Th1 type cytokine, at least one Th2 type cytokine, at least one Th17 type cytokine, at least two TNFR superfamily members, at least two chemokines/adhesion molecules, at least two regulatory mediators, and at least two other SLE mediators; and   (b) one or more reagents for assessing anti-nuclear antibody (ANA) testing and/or anti-extractable nuclear antigen (anti-ENA) in a biological sample.   
     
     
         32 - 35 . (canceled)