Compositions comprising soluble cd84 or anti-cd84 antibodies and methods for diagnosing and treating b-cll

Abstract

A method of diagnosing B-CLL in a subject in need thereof is provided. The method comprising determining in a biological sample of the subject a level of CD84 isoform C (SEQ ID NO: 30), wherein an increase in the level of the CD84 isoform C (SEQ ID NO: 30) beyond a predetermined threshold with respect to a level of the CD84 in a biological sample from a healthy individual is indicative of the B-CLL.

What is claimed is: 
     
         1 . A method of inducing apoptosis in B cells of a subject having B-CLL, the method comprising administering to the subject a therapeutically effective amount of an agent which downregulates an expression level and/or an activity of CD84, thereby inducing apoptosis in B cells of the subject. 
     
     
         2 . A method of treating B-CLL in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent which downregulates an expression level and/or an activity of CD84, thereby treating B-CLL. 
     
     
         3 . A method of diagnosing and treating B-CLL in a subject in need thereof, the method comprising:
 (a) detecting expression of CD84 isoform C (SEQ ID NO: 30) in a biological sample from the subject;   (b) diagnosing the subject with B-CLL when an increase in a level of said CD84 isoform C (SEQ ID NO: 30) is detected beyond a predetermined threshold with respect to said level of said CD84 isoform C in a biological sample from a healthy individual; and   (c) administering to the diagnosed subject a therapeutically effective amount of an agent which downregulates an expression level and/or an activity of CD84, thereby diagnosing and treating B-CLL in the subject.   
     
     
         4 . The method of  claim 3 , wherein said biological sample comprises B cells and wherein said detecting is in said B cells. 
     
     
         5 . The method of  claim 3 , further comprising isolating B cells from said biological sample prior to said detecting. 
     
     
         6 . The method of  claim 3 , wherein said detecting is effected at the mRNA level. 
     
     
         7 . The method of  claim 3 , wherein said detecting is effected at the protein level. 
     
     
         8 . The method of  claim 3 , further comprising corroborating the diagnosis using a diagnostic assay selected from surface marker expression distinctive of said CD84 isoform c, karyotype analysis and germline mutations. 
     
     
         9 . The method of  claim 3 , further comprising informing the subject of the disease. 
     
     
         10 . The method of  claim 3 , wherein said agent which downregulates an expression level and/or an activity of CD84 is a CD84 neutralizing antibody. 
     
     
         11 . An isolated polypeptide comprising an amino acid sequence of a soluble CD84, wherein said soluble CD84 binds CD84 expressed on B cells and inhibits its homophilic interaction. 
     
     
         12 . A pharmaceutical composition comprising a soluble CD84, wherein said soluble CD84 binds CD84 expressed on B cells and inhibits its homophilic interaction. 
     
     
         13 . An isolated polynucleotide comprising a nucleic acid sequence encoding the soluble CD84 of  claim 11 . 
     
     
         14 . The isolated polypeptide of  claim 11 , wherein said amino acid sequence of said soluble CD84 is as set forth in SEQ ID NO: 2. 
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein said amino acid sequence of said soluble CD84 is as set forth in SEQ ID NO: 2. 
     
     
         16 . The method of  claim 1 , wherein said agent which downregulates said expression level and/or said activity of CD84 is a nucleic acid agent for silencing CD84 expression. 
     
     
         17 . The method of  claim 2 , wherein said agent which downregulates said expression level and/or said activity of CD84 is a nucleic acid agent for silencing CD84 expression.