Compositions and methods for diagnosing or treating psoriasis

Abstract

The present invention provides nucleic acid molecules, polypeptides, antibodies and methods for the diagnosis and/or treatment of psoriasis.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:  
     
         1 . An isolated genomic DNA molecule that encodes a polypeptide that is at least 70% identical to the 19.5 polypeptide of SEQ ID NO:2.  
     
     
         2 . An isolated genomic DNA molecule of  claim 1 , wherein the encoded polypeptide is at least 80% identical to the 19.5 polypeptide of SEQ ID NO:2.  
     
     
         3 . An isolated genomic DNA molecule of  claim 1 , wherein the encoded polypeptide is at least 90% identical to the 19.5 polypeptide of SEQ ID NO:2.  
     
     
         4 . An isolated genomic DNA molecule of  claim 1 , wherein the encoded polypeptide is at least 95% identical to the 19.5 polypeptide of SEQ ID NO:2.  
     
     
         5 . An isolated genomic DNA molecule that hybridizes to the cDNA molecule having the sequence set forth in SEQ ID NO:1, or to the complement thereof, under stringent conditions of 1× SSC at 55° C.  
     
     
         6 . An isolated genomic DNA molecule of  claim 5  which hybridizes to the cDNA molecule having the sequence set forth in SEQ ID NO:1, or to the complement thereof, under stringent conditions of 0.1× SSC at 60° C.  
     
     
         7 . An isolated nucleic acid molecule that comprises a nucleic acid molecule that encodes a 19.5 polypeptide, wherein said encoded 19.5 polypeptide is at least 70% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2, and said nucleic acid molecule encoding said 19.5 polypeptide is operably linked to a skin-specific promoter.  
     
     
         8 . The isolated nucleic acid molecule of  claim 7  wherein said encoded 19.5 polypeptide is at least 80% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         9 . The isolated nucleic acid molecule of  claim 7  wherein said encoded 19.5 polypeptide is at least 90% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         10 . The isolated nucleic acid molecule of  claim 7  wherein said encoded 19.5 polypeptide is at least 95% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         11 . The isolated nucleic acid molecule of  claim 7  wherein said skin-specific promoter is active in the epithelium.  
     
     
         12 . A vector comprising a nucleic acid molecule that encodes a polypeptide that is at least 70% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         13 . A vector of  claim 12  wherein said encoded polypeptide is at least 80% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         14 . A vector of  claim 12  wherein said encoded polypeptide is at least 90% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         15 . A vector of  claim 12  wherein said encoded polypeptide is at least 95% identical to the 19.5 polypeptide having the sequence set forth in SEQ ID NO:2.  
     
     
         16 . A vector of  claim 12  wherein said nucleic acid molecule is operably linked to a skin-specific promoter.  
     
     
         17 . An isolated antibody that binds specifically to a polypeptide consisting of an amino acid sequence that is at least 70% identical to the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         18 . An isolated antibody of  claim 17  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 80% identical to the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         19 . An isolated antibody of  claim 17  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         20 . An isolated antibody of  claim 17  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         21 . An isolated antibody of  claim 17  that binds specifically to a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         22 . An isolated antibody of  claim 17  wherein said antibody is a polyclonal antibody.  
     
     
         23 . An isolated antibody of  claim 17  wherein said antibody is a monoclonal antibody.  
     
     
         24 . An isolated antibody of  claim 17  wherein said antibody is a CDR-grafted antibody.  
     
     
         25 . A host cell comprising a vector of any one of claims  12 - 16 .  
     
     
         26 . A method of diagnosing or predicting the susceptibility to psoriasis in an individual, said method comprising: 
 (a) obtaining a sample from an individual;    (b) determining an expression level of a 19.5 polypeptide in said sample; and    (c) diagnosing or predicting the susceptibility of said individual to psoriasis based on the presence or amount of expression of said polypeptide.    
     
     
         27 . The method of  claim 26  wherein said 19.5 polypeptide is at least 70% identical to the 19.5 polypeptide having the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         28 . A method of diagnosing or predicting the susceptibility to psoriasis in an individual, said method comprising: 
 (a) obtaining a sample from an individual;    (b) determining an expression level of a nucleic acid molecule that is at least 70% identical to the nucleic acid molecule having the sequence set forth in SEQ ID NO:1; and    (c) diagnosing or predicting the susceptibility of said individual to psoriasis based on the presence or amount of expression of said nucleic acid molecule.    
     
     
         29 . A method of treating or reducing the progression of psoriasis, comprising administering to an individual having psoriasis an inhibitory amount of a selective inhibitor of a 19.5 polypeptide, wherein said inhibitory amount causes a reduction in the amount or activity of the 19.5 polypeptide.  
     
     
         30 . A method of making an isolated 19.5 polypeptide comprising: 
 (a) culturing a host cell of  claim 25  under conditions such that said 19.5 polypeptide is expressed; and    (b) recovering said expressed polypeptide.    
     
     
         31 . A method for identifying a binding partner to a 19.5 polypeptide comprising: 
 (a) contacting a 19.5 polypeptide with a binding partner; and    (b) determining whether the binding partner affects an activity of the polypeptide.    
     
     
         32 . An isolated cDNA molecule that encodes a 19.5-like polypeptide, wherein said 19.5-like polypeptide is at least 70% identical to the 19.5-like polypeptide having the sequence set forth in SEQ ID NO:4.  
     
     
         33 . The 19.5-like cDNA of  claim 32  wherein said 19.5-like polypeptide is at least 80% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         34 . The 19.5-like cDNA of  claim 32  wherein said 19.5-like polypeptide is at least 90% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         35 . The 19.5-like cDNA of  claim 32  wherein said 19.5-like polypeptide is at least 95% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         36 . The isolated cDNA molecule of  claim 32  wherein said 19.5-like polypeptide consists of the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         37 . The isolated cDNA molecule of  claim 32 , wherein said isolated cDNA molecule is full-length.  
     
     
         38 . An isolated cDNA molecule that encodes a 19.5-like polypeptide and that hybridizes to the nucleic acid molecule of SEQ ID NO:3, or to the complement thereof, under stringent conditions of 1× SSC at 55° C.  
     
     
         39 . An isolated cDNA molecule of  claim 38 , wherein said isolated nucleic acid molecule hybridizes to the nucleic acid molecule of SEQ ID NO:3, or to the complement thereof, under stringent conditions of 0.1× SSC at 55° C.  
     
     
         40 . An isolated nucleic acid molecule that comprises a nucleic acid molecule that encodes a 19.5-like polypeptide that is at least 70% identical to the 19.5-like polypeptide having the amino sequence set forth in SEQ ID NO:4, said nucleic acid molecule encoding a 19.5-like polypeptide being operably linked to a skin-specific promoter.  
     
     
         41 . The isolated nucleic acid molecule of  claim 40  wherein said 19.5-like polypeptide is at least 80% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         42 . The isolated nucleic acid molecule of  claim 40  wherein said 19.5-like polypeptide is at least 90% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         43 . The isolated nucleic acid molecule of  claim 40  wherein said 19.5-like polypeptide is at least 95% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         44 . The isolated nucleic acid molecule of  claim 40  wherein said 19.5-like polypeptide consists of the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         45 . An isolated nucleic acid molecule comprising a cDNA molecule that encodes a 19.5-like polypeptide that is at least 70% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4, said 19.5-like cDNA being operably linked to a skin-specific promoter.  
     
     
         46 . A vector comprising a cDNA molecule encoding a 19.5-like polypeptide that is at least 70% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         47 . A vector of  claim 46  wherein said 19.5-like polypeptide is at least 80% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         48 . A vector of  claim 46  wherein said 19.5-like polypeptide is at least 90% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         49 . A vector of  claim 46  wherein said 19.5-like polypeptide is at least 95% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         50 . A vector of  claim 46  wherein said 19.5-like cDNA molecule is operably linked to a skin-specific promoter.  
     
     
         51 . An isolated antibody that binds specifically to a polypeptide consisting of an amino acid sequence that is at least 70% identical to the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         52 . An isolated antibody of  claim 51  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 80% identical to the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         53 . An isolated antibody of  claim 51  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         54 . An isolated antibody of  claim 51  wherein said antibody binds specifically to a polypeptide consisting of an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         55 . An isolated antibody of  claim 51  wherein said isolated antibody binds specifically to the polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         56 . The isolated antibody of  claim 51  wherein said antibody is a polyclonal antibody.  
     
     
         57 . The isolated antibody of  claim 51  wherein said antibody is a monoclonal antibody.  
     
     
         58 . The isolated antibody of  claim 51  wherein said antibody is a CDR-grafted antibody.  
     
     
         59 . A host cell comprising a vector of any one of claims  46 - 50 .  
     
     
         60 . A method of diagnosing or predicting the susceptibility to psoriasis in an individual, said method comprising: 
 (a) obtaining a sample from an individual;    (b) determining an expression level of a 19.5-like polypeptide in said sample; and    (c) diagnosing or predicting the susceptibility of said individual to psoriasis based on the presence or amount of expression of said polypeptide.    
     
     
         61 . A method of claim  60  wherein said 19.5-like polypeptide is at least 70% identical to the 19.5-like polypeptide having the amino acid sequence set forth in SEQ ID NO:4.  
     
     
         62 . A method of diagnosing or predicting the susceptibility to psoriasis in an individual, said method comprising: 
 (a) obtaining a sample from an individual;    (b) determining an expression level of a nucleic acid molecule that is at least 70% identical to the nucleic acid molecule having the sequence set forth in SEQ ID NO:3; and    (c) diagnosing or predicting the susceptibility of said individual to psoriasis based on the presence or amount of expression of said nucleic acid molecule.    
     
     
         63 . A method for ameliorating the symptoms and/or progression of psoriasis, comprising administering to an individual having psoriasis an inhibitory amount of a selective inhibitor of a 19.5-like polypeptide, wherein said inhibitory amount causes a reduction in the amount or activity of the 19.5-like polypeptide.  
     
     
         64 . A method of making an isolated 19.5-like polypeptide comprising: 
 (a) culturing a host cell of  claim 59  under conditions such that said 19.5-like polypeptide is expressed; and    (b) recovering said expressed polypeptide.    
     
     
         65 . A method for identifying a binding partner to a 19.5-like polypeptide comprising: 
 (a) contacting a 19.5-like polypeptide with a binding partner; and    (b) determining whether the binding partner affects an activity of the polypeptide.