Compositions and methods for characterizing arthritic conditions

Abstract

The present invention relates to autoantibodies against 14-3-3 proteins or circulating immune complexes thereof and the detection of such for the diagnosis and prognosis of an arthritic condition.

We claim: 
     
         1 . A method for evaluating an arthritic condition in a subject, comprising: a) providing a sample from a subject suspected of having an arthritic condition; b) detecting the presence of an autoantibody against, or an immune complex with, at least one 14-3-3 protein or fragment thereof in said sample; wherein the presence of said autoantibody or immune complex is indicative of an arthritic condition in the subject. 
     
     
         2 . The method according to  claim 1 , wherein said detecting step further comprises measuring the amount of said autoantibody or immune complex and comparing it against the amount of autoantibody or immune complex in a normal control sample, an arthritic control sample, or in a previous sample from the same subject 
     
     
         3 . The method according to  claim 1 , wherein the detecting step comprises contacting the biological sample with at least one 14-3-3 protein or fragment thereof. 
     
     
         4 . The method according to  claim 3 , wherein said 14-3-3 protein is 14-3-3 eta or 14-3-3 gamma, or a fragment thereof. 
     
     
         5 . The method according to  claim 1 , wherein said 14-3-3 protein comprises at least one 14-3-3 eta epitope. 
     
     
         6 . The method according to  claim 5  wherein said at least one 14-3-3 eta epitope is shared with at least one other 14-3-3 protein isoform. 
     
     
         7 . The method according to  claim 5 , wherein said other 14-3-3 protein isoform is 14-3-3 gamma. 
     
     
         8 . The method according to  claim 5 , wherein said 14-3-3 eta epitope is unique to 14-3-3 eta. 
     
     
         9 . The method according to any one of the preceding claims, wherein the biological sample is selected from the group consisting of blood, synovial fluid, plasma, serum or tissue. 
     
     
         10 . The method according to any one of the preceding claims, wherein the 14-3-3 protein or fragment thereof is detectably labeled with a label selected from the group consisting of a radioactive label, a luminescent label, and a fluorescent label, and an enzyme. 
     
     
         11 . The method according to any one of the preceding claims, wherein the 14-3-3 protein or fragment thereof is bound to a solid support. 
     
     
         12 . The method according to any one of the preceding claims, wherein the autoantibody is detected by an ELISA assay. 
     
     
         13 . The method according to any one of the preceding claims, wherein said detection occurs by chemiluminesence. 
     
     
         14 . The method of  claim 2 , wherein an increased level of said autoantibody against, or an immune complex with, at least one 14-3-3 protein or fragment thereof in said sample in comparison with the normal control sample is a diagnostic indicator of arthritis in said subject. 
     
     
         15 . The method of  claim 2 , wherein a relative level of said autoantibody against, or an immune complex with, at least one 14-3-3 protein or fragment thereof in said sample in comparison with the arthritic control sample is a prognostic indicator of arthritis in said subject. 
     
     
         16 . The method of  claim 2 , wherein the relative level of said autoantibody against, or an immune complex with, at least one 14-3-3 protein or fragment thereof in said sample in comparison with the previous sample from the same subject is indicative of the efficacy of a therapeutic regimen. 
     
     
         17 . A kit for detecting the presence of an autoantibody to at least one 14-3-3 protein or fragment thereof in a sample, comprising at least one 14-3-3 protein or fragment thereof and a secondary reagent. 
     
     
         18 . The kit according to  claim 17 , wherein said at least one 14-3-3 protein or fragment thereof is bound to a solid support 
     
     
         19 . The kit according to  claim 17 , wherein said at least one 14-3-3 protein is 14-3-3 gamma or 14-3-3 eta, or a fragment thereof. 
     
     
         20 . The kit according to  claim 17 , wherein said 14-3-3 protein or fragment thereof comprises at least one 14-3-3 eta epitope. 
     
     
         21 . The kit according to  claim 20 , wherein said at least one 14-3-3 eta epitope is shared with at least one other 14-3-3 protein isoform. 
     
     
         22 . The kit according to  claim 21 , wherein said other 14-3-3 protein isoform is 14-3-3 gamma. 
     
     
         23 . The kit according to  claim 21 , wherein said 14-3-3 eta epitope is unique to 14-3-3 eta. 
     
     
         24 . A method for determining the subtype of arthritis in a patient comprising (a) providing a first sample from a subject suspected of having an arthritic condition; (b) detecting the presence of an autoantibody against, or an immune complex with, at least one 14-3-3-protein or fragment thereof in said sample; (c) measuring the amount of said autoantibody or immune complex and comparing it against the amount of autoantibodies against, or immune complexes with, 14-3-3 in a second biological sample from a second subject whose subtype of arthritis is known and/or previously-established, wherein such comparison determines the subtype of arthritis for the first subject. 
     
     
         25 . The method of  claim 24 , wherein similar amounts of said autoantibody or immune complex between the first and second samples indicates that the first subject has the same subtype of arthritis as the second subject. 
     
     
         26 . The method of  claim 24 , wherein dissimilar amounts of said autoantibody or immune complex between the first and second samples indicates that the first subject has a different subtype of arthritis than the second subject.