CXCR4 as a Susceptibility Locus in Juvenile Idiopathic Arthritis (JIA) and Methods of Use Thereof for the Treatment and Diagnosis of the Same

Abstract

Compositions and methods useful for the diagnosis and treatment of juvenile idiopathic arthritis are disclosed.

What is claimed is: 
     
         1 . A method for detecting an increased risk for developing juvenile idiopathic arthritis (JIA) in a test subject, comprising,
 a) obtaining a nucleic acid sample from said subject and determining whether said sample contains at least one SNP or mutation identified in the CXCR4 locus wherein if said SNP or mutation is detected, said patient has an increased risk for developing JIA, wherein said SNP or mutation containing nucleic acid is selected from the group consisting of
 i) SNPs provided in Table 4; 
 ii) a SNP in LD with those listed in Table 4; 
 iii) a non synonymous mutation; and 
 iv) a stop gain mutation. 
   
     
     
         2 . The method as claimed in  claim 1 , wherein the target nucleic acid is amplified prior to detection. 
     
     
         3 . The method of  claim 1 , wherein the step of detecting the presence of said SNP or mutation is performed using a process selected from the group consisting of detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, single base primer extension reaction, and sequencing of an amplified polynucleotide. 
     
     
         4 . The method as claimed in  claim 1 , wherein in the target nucleic acid is DNA. 
     
     
         5 . The method of  claim 1 , wherein nucleic acids comprising said SNP or mutation are obtained from an isolated cell of a human test subject. 
     
     
         6 . A method for identifying therapeutic agents which alter immune cell function or signaling, comprising
 a) providing cells expressing at least one SNP or mutation containing nucleic acid as claimed in  claim 1 ;   b) providing cells which express the cognate wild type sequences corresponding to the SNP or mutation containing nucleic acid of step a);   c) contacting the cells of steps a) and b) with a test agent and   d) analyzing whether said agent alters immune signaling or function of cells of step a) relative to those of step b), thereby identifying agents which alter immune cell signaling or function.   
     
     
         7 . The method of  claim 6  wherein said agent is selected from the group consisting of agents listed in Table 12. 
     
     
         8 . The method of  claim 6  wherein said therapeutic has efficacy for the treatment of JIA or other related aberrant immune dysfunction disorders. 
     
     
         9 . A method for the treatment of JIA in a patient in need thereof comprising administration of an effective amount of the agent identified by  claim 6 . 
     
     
         10 . The method of  claim 9 , wherein said agent modulates the inflammatory process. 
     
     
         11 . The method of  claim 9 , wherein said agent modulates cytokine release. 
     
     
         12 . A multiplex SNP or mutation panel comprising isolated nucleic acids informative of the presence of JIA, wherein said panel contains the nucleic acids provided in Table 4 or a SNV selected from the group consisting of NM — 001008540:c.C1049A:p.S350Y, NM — 001008540:c.A169C:p.I57L, NM — 001008540:c.C19G:p.L7V, and NM — 001008540:c.T14A:p.L5X stop codon. 
     
     
         13 . A vector comprising at least one of the SNP-containing nucleic acids of  claim 12 . 
     
     
         14 . A host cell comprising the vector of  claim 13 . 
     
     
         15 . A solid support comprising the JIA related SNP containing nucleic acid of  claim 12 . 
     
     
         16 . A kit for performing the method of  claim 1 , comprising a multiplex SNP panel comprising nucleic acids informative of the presence of JIA in an isolated nucleic acid sample, wherein said panel contains the nucleic acids provided in Table 4. 
     
     
         17 . The kit of  claim 16 , wherein said panel is affixed to a solid support. 
     
     
         18 . The kit of  claim 16 , wherein said panel is provided in silico.