Methods and compositions for detecting autoimmune disorders

Abstract

The invention provides methods and compositions useful for detecting autoimmune disorders.

1 - 19 . (canceled) 
     
     
         20 . A method of identifying a metric value correlated with presence and/or extent of an autoimmune disorder in a subject or sample, said method comprising:
 (a) estimating a group of probesets that is collectively associated with a pattern wherein expression of genes represented by the probesets is associated with a disease characteristic;   (b) generating a weighting factor that weight probesets in accordance with a scale reflecting extent of match of each individual probeset to trend of the group of probesets, and calculating the correlation coefficient of each probeset's profile to the mean profile calculated;   (c) determining a scaling factor, wherein the scaling factor is the value required to scale individual probesets to 1;   (d) multiplying the scaling factor by the weighting factor to generate a composite factor   (e) multiplying a normal blood sample's signatures with the composite factor, and averaging the resulting values across both probesets and samples to generate an average value, and inverting the average value to yield a global scaling factor;   (f) multiplying each weighting factor by the global scaling factor to obtain a vector of scalar values, and multiplying the scalar values by an expression signature from a sample of interest, and averaging the resulting values to yield a single metric that is indicative of degree of gene expression associated with Type I interferons in the sample.   
     
     
         21 . The method of  claim 20 , wherein in step (a), the group of probesets comprises probesets that include, or cluster around, the core most-tightly-correlated pair of probesets in subcluster associated with a disease characteristic. 
     
     
         22 . The method of  claim 20 , wherein in step (b), the factor is generated by transforming expression data of the group of probesets into z-scores comprising mean scaling to 1, base-2 log transformation, then scaling to a standard deviation of the mean of 1. 
     
     
         23 . The method of  claim 20 , wherein in step (e), the global scaling factor is useful for transforming output of the average of probesets from a sample of interest into a metric, wherein the metric is 1 if the sample is from a normal, healthy subject. 
     
     
         24 . The method of  claim 20 , wherein the group of probesets comprises at least 2 of those listed in Table 1, 2, and/or 3. 
     
     
         25 . The method of  claim 20 , wherein the group of probesets comprises those listed in Table 1, 2, and/or 3. 
     
     
         26 . A method of predicting responsiveness of a human subject with systemic lupus erythematosus (SLE) to autoimmune disease therapy, said method comprising
 (a) performing a nucleic acid-based detection assay to detect mRNA expression level of at least three genes comprising a three gene combination listed in Table 4B in cells of a blood sample from the human subject, wherein the at least three genes do not comprise OASL, IRF7 and PARP9;   (b) determining that the cells from the human subject express the at least three genes comprising the three gene combination at a level greater than the expression level of the respective genes in cells of a blood sample from a healthy human control; thereby predicting that the human subject will have a favorable response to the autoimmune disease therapy, wherein the autoimmune disease therapy comprises an anti-interferon-alpha antibody or an anti-interferon-alpha receptor antibody.   
     
     
         27 . A method of treating a human subject having systemic lupus erythematosus (SLE), comprising:
 (a) performing a nucleic acid-based detection assay to detect mRNA expression levels of at least three genes comprising a three gene combination listed in Table 4B in cells of a blood sample from the human subject, wherein the at least three genes do not comprise OASL, IRF7 and PARP9;   (b) determining that the cells from the human subject express the at least three genes comprising the three gene combination at a level greater than the expression level of the respective genes in cells of a blood sample from a healthy human control; and   (c) administering an effective amount of an anti-interferon-alpha antibody or an anti-interferon-alpha receptor antibody to the human subject expressing the at least three genes comprising the three gene combination at a level greater than the expression level of the respective genes in cells of a blood sample from a healthy human control, thereby treating SLE in the human subject.   
     
     
         28 . The method of  claim 26 , wherein the three gene combination comprises any three genes of the group consisting of EPSTI1, HERC5, TYKI, IFI44L, CIG5, and IFI44. 
     
     
         29 . The method of  claim 26 , wherein the three gene combination is a combination selected from the group consisting of: 
       
         
           
                 
                 
                 
                 
                 
               
                     
                     
                 
                     
                   (1) 
                   EPSTI1, 
                   HERC, and 
                   TYKI; 
                 
                     
                   (2) 
                   EPSTI1, 
                   HERC, and 
                   IFI44L; 
                 
                     
                   (3) 
                   EPSTI1, 
                   HERC, and 
                   CIG5; 
                 
                     
                   (4) 
                   EPSTI1, 
                   HERC, and 
                   IFI44; 
                 
                     
                   (5) 
                   HERC, 
                   TYKI, and 
                   IFI44L; 
                 
                     
                   (6) 
                   HERC, 
                   TYKI, and 
                   CIG5; 
                 
                     
                   (7) 
                   HERC, 
                   TYKI, and 
                   IFI44; 
                 
                     
                   (8) 
                   TYKI, 
                   IFI44L, and 
                   CIG5; 
                 
                     
                   (9) 
                   TYKI, 
                   IFI44L, and 
                   IFI44; 
                 
                     
                   (10) 
                   TYKI, 
                   IFI44L, and 
                   EPSTI1; 
                 
                     
                   (11) 
                   IFI44L, 
                   CIG5, and 
                   IFI44; 
                 
                     
                   (12) 
                   IFI44L, 
                   CIG5, and 
                   EPSTI1; 
                 
                     
                   (13) 
                   IFI44L, 
                   CIG5, and 
                   HERC; 
                 
                     
                   (14) 
                   IFI44L, 
                   CIG5, and 
                   TYKI; 
                 
                     
                   (15) 
                   CIG5, 
                   IFI44, and 
                   EPSTI1; 
                 
                     
                   (16) 
                   CIG5, 
                   IFI44, and 
                   HERC, 
                 
                     
                   (17) 
                   CIG5, 
                   IFI44, and 
                   TYKI, 
                 
                     
                   (18) 
                   IFI44, 
                   EPSTI1, and 
                   TYKI, 
                 
                     
                   (19) 
                   IFI44, 
                   EPSTI1, and 
                   IFI44L, and 
                 
                     
                   (20) 
                   IFI44, 
                   EPSTI1, and 
                   CIG5. 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         30 . The method of  claim 26 , wherein the three gene combination is EPSTI1, HERC5 and TYKI. 
     
     
         31 . The method of  claim 26 , wherein the performing a nucleic acid-based detection assay comprises performing a nucleic acid hybridization assay. 
     
     
         32 . The method of  claim 26 , wherein the performing a nucleic acid-based detection assay comprising performing a nucleic acid amplification assay. 
     
     
         33 . The method of  claim 26 , wherein the autoimmune disease therapy comprises an anti-interferon-alpha antibody. 
     
     
         34 . The method of  claim 27 , wherein the three gene combination comprises any three genes of the group consisting of EPSTI1, HERC5, TYKI, IFI44L, CIG5, and IFI44. 
     
     
         35 . The method of  claim 27 , wherein the three gene combination is EPSTI1, HERC5 and TYKI. 
     
     
         36 . The method of  claim 27 , wherein the performing a nucleic acid-based detection assay comprises performing a nucleic acid hybridization assay. 
     
     
         37 . The method of  claim 27 , wherein the performing a nucleic acid-based detection assay comprising performing a nucleic acid amplification assay. 
     
     
         38 . The method of  claim 27 , wherein step (c) comprises administering the anti-interferon-alpha antibody to the human subject. 
     
     
         39 . The method of  claim 38 , wherein step (c) comprises administering the anti-interferon-alpha antibody to the human subject in combination with a second therapeutic agent. 
     
     
         40 . The method of  claim 39 , wherein the second therapeutic agent is a steroid.