Vh4 codon signature for multiple sclerosis

Abstract

The present invention provides for the diagnosis and prediction of multiple sclerosis (MS) in subject utilizing a unique a codon signature in VH4 expressiong B cells that has now been associated with MS and not with any other autoimmune disease.

What is claimed is: 
     
         1 . A method for identifying a human subject having or at risk of developing multiple sclerosis (MS) comprising assessing the VH4 structure of a VH4-expressing B-cell from said subject, wherein the presence of a codon signature associated with MS identifies said subject as having or at risk of developing MS. 
     
     
         2 . The method of  claim 1 , wherein said codon signature comprises a mutation at codon 31B, 56 and/or 81. 
     
     
         3 . The method of  claim 2 , wherein said codon signature comprises mutations at each of 31B, 56 and 81. 
     
     
         4 . The method of  claim 2  or  3 , wherein said codon signature further comprises mutations at one or more of codons 32, 40, 57, 60 and 89. 
     
     
         5 . The method of  claim 4 , wherein said codon signature comprises mutations at each of codons 31B, 32, 40, 56, 57, 60, 81 and 89. 
     
     
         6 . The method of  claim 1 , wherein said codon signature comprises a mutation at codons 31B, 40, 56, 57, 81 and/or 89. 
     
     
         7 . The method of  claim 6 , wherein said codon signature comprises a mutation at each of codons 31B, 40, 56, 57, 81 and 89. 
     
     
         8 . The method of  claim 1 , further comprising assessing one or more traditional MS risk factors. 
     
     
         9 . The method  claim 1 , wherein assessing comprises sequencing. 
     
     
         10 . The method of  claim 1 , wherein assessing comprises PCR. 
     
     
         11 . The method of  claim 1 , wherein said B-cell is obtained from cerebrospinal fluid (CSF). 
     
     
         12 . The method of  claim 11 , further comprising assessing J chain usage, J chain length and/or CDR3 length. 
     
     
         13 . The method of  claim 1 , wherein said B-cell is obtained from peripheral blood. 
     
     
         14 . The method of  claim 13 , further comprising assessing J chain usage, J chain length and/or CDR3 length. 
     
     
         15 . The method of  claim 1 , further comprising making a treatment decision based on the presence of said codon signature. 
     
     
         16 . A method of screening for an agent useful in treating multiple sclerosis (MS) comprising:
 (a) providing an antibody produced by a VH4-expressing B-cell, said antibody comprising mutations at three or more codons selected from the group consisting of 31B, 32, 40, 56, 57, 60, 81 and 89;   (b) contacting said antibody with a candidate ligand; and   (c) assessing binding of said candidate ligand to said antibody,   
       wherein binding of said candidate ligand to said antibody identifies said candidate ligand as useful in treating MS. 
     
     
         17 . The method of  claim 16 , wherein said candidate ligand is a peptide or a peptoid. 
     
     
         18 . A method of treating a subject having or at risk of developing MS comprising administering to said subject a ligand that binds to an antibody VH-4 antibody comprising mutations at three or more codons selected from the group consisting of 31B, 32, 40, 56, 57, 60, 81 and 89. 
     
     
         19 . The method of  claim 18 , wherein said ligand is a peptide or a peptoid. 
     
     
         20 . The method of  claim 18 , wherein said ligand is linked to a toxin or B-cell antagonist.