Peptides immunoreactive with autoantibodies from patients suffering from rheumatoid arthritis

Abstract

The invention relates to a peptide derived from an antigen recognized by autoantibodies, which peptide is reactive with autoimmune antibodies from a patient suffering from rheumatoid arthritis. The peptide according to the invention possesses a modified arginine residue. The invention also relates to antibodies against the peptide and a method of detecting autoimmune antibodies.

1 . An artificial antigen consisting of a recombinant or synthetic polypeptide which comprises a modified amino acid sequence derived from protein having the amino acid sequence of SEQ ID NO: 17 or a fragment thereof by replacing at least one arginine residue with a citrulline residue,
 which antigen is specifically immunoreactive with anti-filaggrin antibodies present in the serum of subjects suffering from rheumatoid arthritis.   
     
     
         2 . The antigen of  claim 1  wherein one arginine is replaced by citrulline. 
     
     
         3 . The antigen of  claim 1  wherein two or more arginines are replaced by citrulline. 
     
     
         4 . A method to detect rheumatoid arthritis by detecting an autoimmune antibody in the serum of a subject,
 said method comprising contacting the antigen of  claim 1  with said serum and detecting the presence or absence of a complex between the antigen and an antibody, wherein the presence of said complex detects rheumatoid arthritis.   
     
     
         5 . The method of  claim 4  wherein the detecting comprises use of an antihuman antibody. 
     
     
         6 . The method of  claim 4  wherein the detecting comprises use of an enzyme-linked immunosorbent assay (ELISA). 
     
     
         7 . The method of  claim 4  wherein said contacting is with more than one artificial antigen consisting of a recombinant or synthetic polypeptide which comprises a modified amino acid sequence derived from filaggrin by replacing at least one arginine residue with a citrulline residue of a wild type filaggrin amino acid sequence,
 which antigen is specifically immunoreactive with anti-filaggrin antibodies present in the serum of subjects suffering from rheumatoid arthritis. 
 
     
     
         8 . An isolated antibody crossreactive with an antibody raised against an antigen which is a synthetic peptide which comprises an amino acid sequence that is the same as that of a fragment having no more than 19 amino acids of the amino acid sequence of SEQ ID NO:17 and having sufficient length to act as an epitope for antibody binding, except that said peptide has at least one arginine residue of SEQ ID NO:17 replaced by a citrulline residue. 
     
     
         9 . The antibody of  claim 8  wherein said antigen is in cyclic form. 
     
     
         10 . The antibody of  claim 8  wherein said antigen contains at least two cysteines. 
     
     
         11 . The antibody of  claim 8  which is a monoclonal antibody. 
     
     
         12 . The antibody of  claim 9  which is a monoclonal antibody. 
     
     
         13 . The antibody of  claim 8  which is labeled. 
     
     
         14 . The antibody of  claim 9  which is labeled. 
     
     
         15 . The antibody of  claim 8  which is coupled to a carrier. 
     
     
         16 . The antibody of  claim 9  which is coupled to a carrier.