Polynucleotides and polypeptides associated with the development of rheumatoid arthritis

Abstract

The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

1 . An assay for identifying a compound that modulates the activity of a gene associated with rheumatoid arthritis, comprising:
 (a) providing a cell expressing a gene associated with rheumatoid arthritis, wherein the nucleic acid sequence of said gene associated with rheumatoid arthritis is at least 95% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NO:41 and SEQ ID NO:61,   (b) contacting said cell expressing said gene associated with rheumatoid arthritis with a test compound; and   (c) determining whether said test compound modulates the activity of said gene associated with rheumatoid arthritis.   
     
     
         2 . The assay of  claim 1 , wherein said assay is a cell-based assay. 
     
     
         3 . The assay of  claim 1 , wherein said assay is a cell-free assay. 
     
     
         4 . The assay of  claim 3 , wherein said cell-free assay is a ligand-binding assay. 
     
     
         5 . The assay of  claim 1 , wherein said test compound modulates the activity of said gene associated with rheumatoid arthritis. 
     
     
         6 . The assay of  claim 1 , wherein said test compound is an antagonist of a gene associated with rheumatoid arthritis. 
     
     
         7 . The assay of  claim 1 , wherein said test compound is an agonist of a gene associated with rheumatoid arthritis. 
     
     
         8 . The assay of  claim 1 , wherein said test compound binds to said gene associated with rheumatoid arthritis. 
     
     
         9 . The assay of  claim 1 , wherein said assay is useful for identifying compounds which are useful for the treatment of rheumatoid arthritis. 
     
     
         10 . A method for the treatment of rheumatoid arthritis, comprising:
 (a) identifying a patient suffering from rheumatoid arthritis; and   (b) administering to said patient a therapeutically effective amount of a modulator of a gene associated with rheumatoid arthritis,   wherein said gene associated with rheumatoid arthritis has a nucleic acid sequence which is at least 95% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NO:41 and SEQ ID NO:61.   
     
     
         11 . The method of  claim 10 , wherein said patient is identified as suffering from rheumatoid arthritis by measuring the expression level of said gene associated with rheumatoid arthritis in said patient. 
     
     
         12 . The method of  claim 10 , wherein said modulator is an antagonist of a gene associated with rheumatoid arthritis. 
     
     
         13 . A method for the treatment of rheumatoid arthritis, comprising:
 (a) identifying a patient suffering from rheumatoid arthritis; and   (b) administering to said patient suffering from rheumatoid arthritis a therapeutically effective amount of a modulator of a polypeptide associated with rheumatoid arthritis,   wherein said polypeptide associated with rheumatoid arthritis has an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:42 and SEQ ID NO:62.   
     
     
         14 . The method of  claim 13 , wherein said patient is identified as suffering from rheumatoid arthritis by measuring the expression level of said polypeptide associated with rheumatoid arthritis. 
     
     
         15 . The method of  claim 13 , wherein said modulator is an antagonist of a polypeptide associated with rheumatoid arthritis. 
     
     
         16 . A method for the prevention of rheumatoid arthritis, comprising:
 (a) identifying a patient at risk for rheumatoid arthritis; and   (b) administering to said patient at risk for rheumatoid arthritis a therapeutically effective amount of a modulator of a gene associated with rheumatoid arthritis,   wherein said gene associated with rheumatoid arthritis has a nucleic acid sequence which is at least 95% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NO:41 and SEQ ID NO:61.   
     
     
         17 . The method of  claim 16 , wherein said patient is identified as being at risk for rheumatoid arthritis by measuring the expression level of said gene associated with rheumatoid arthritis in said patient. 
     
     
         18 . The method of  claim 16 , wherein said modulator is an antagonist of said gene associated with rheumatoid arthritis. 
     
     
         19 . A method for the prevention of rheumatoid arthritis, comprising:
 (a) identifying a patient at risk for rheumatoid arthritis; and   (b) administering to said patient at risk for rheumatoid arthritis a therapeutically effective amount of a modulator of a polypeptide associated with rheumatoid arthritis,   wherein said polypeptide associated with rheumatoid arthritis has an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:42 and SEQ ID NO:62.   
     
     
         20 . The method of  claim 19 , wherein said patient is identified as being at risk for rheumatoid arthritis by measuring the expression level of said polypeptide associated with rheumatoid arthritis in said patient. 
     
     
         21 . The method of  claim 19 , wherein said modulator is an antagonist of said polypeptide associated with rheumatoid arthritis. 
     
     
         22 . A compound useful for the treatment of rheumatoid arthritis, wherein said compound is identified by:
 (a) providing a cell expressing a gene associated with rheumatoid arthritis, wherein said gene associated with rheumatoid arthritis has a nucleic acid sequence which is at least 95% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NO:41 and SEQ ID NO:61;   (b) contacting said cell expressing said gene associated with rheumatoid arthritis with said compound; and   (c) determining whether said compound modulates the activity of said gene associated with rheumatoid arthritis.   
     
     
         23 . The compound of  claim 22 , wherein said compound is an antagonist of said gene associated with rheumatoid arthritis. 
     
     
         24 . The compound of  claim 22 , wherein said compound is an agonist of said gene associated with rheumatoid arthritis. 
     
     
         25 . A compound useful for the treatment of rheumatoid arthritis, wherein said compound is identified by:
 (a) providing a cell expressing a polypeptide associated with rheumatoid arthritis,   
       wherein said polypeptide associated with rheumatoid arthritis has an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:42 and SEQ ID NO:62;
 (b) contacting said cell expressing said polypeptide associated with rheumatoid arthritis with said compound; and 
 (c) determining whether said compound modulates the activity of said polypeptide associated with rheumatoid arthritis. 
 
     
     
         26 . The compound of  claim 25 , wherein said compound is an antagonist of said polypeptide associated with rheumatoid arthritis.