Anti-carbamylated protein antibodies and the risk for arthritis

Abstract

Antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the diagnosis and possibly pathogenesis in arthritis. Described are means and methods for determining antibodies against homocitrulline-containing proteins or carbamylated proteins/peptides (anti-CarP) for the classification of individuals suffering from, or at risk of suffering from, arthritis.

What is claimed is: 
     
         1 . A method for classifying an individual that is suffering from, or at risk of suffering from, a form of arthritis, the method comprising determining whether a sample comprising a body fluid of the individual comprises an Anti-Carbamylated Protein (anti-CarP) antibody or an Anti-Carbamylated Fibrinogen (anti-Ca-Fib) antibody. 
     
     
         2 . A method for providing a prognosis for the development of arthritis to an individual suffering from arthritis, the method comprising determining whether a sample comprising a body fluid of the individual comprises an Anti-Carbamylated Protein (anti-CarP) antibody, preferably an Anti-Carbamylated Fibrinogen (anti-Ca-Fib) antibody, and estimating the future severity of the arthritis based on the detection of the anti-CarP and/or anti-Ca-Fib antibody in the sample. 
     
     
         3 . The method according to  claim 2 , wherein the body fluid is a serum sample or a synovial fluid sample. 
     
     
         4 . The method according to  claim 2 , wherein the anti-CarP and/or anti-Ca-Fib antibody is of Ig-subtype IgA or of the Ig-subtype IgG. 
     
     
         5 . The method according to  claim 4 , wherein the method further comprises determining whether a sample comprising a body fluid of the individual comprises an Anti-citrullinated Protein Antibody (ACPA). 
     
     
         6 . The method according to  claim 5 , for determining whether the individual is at risk of suffering from arthritis, and wherein the individual was not suffering from arthritis at the time the fluid sample was obtained. 
     
     
         7 . The method according to  claim 5 , wherein the arthritis comprises rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, osteoarthritis, polymyalgia rheumatica, ankylosing spondylitis, reactive arthritis, gout, pseudogout, autoimmune arthritis, systemic lupus erythematosus, polymyositis, fibromyalgia, Lyme disease, undifferentiated arthritis, non-rheumatoid arthritis, or spondyloarthropathy. 
     
     
         8 . The method according to  claim 7 , wherein the arthritis is rheumatoid arthritis, juvenile arthritis or undifferentiated arthritis. 
     
     
         9 . A kit for detecting anti-CarP antibodies in a body fluid of an individual, the kit comprising a carbamylated protein or peptide, preferably carbamylated fibrinogen or a peptide derived therefrom. 
     
     
         10 . The kit of  claim 9 , further comprising an anti-human IgG antibody and/or an anti-human IgA antibody. 
     
     
         11 . The kit of  claim 10 , wherein the anti-human Ig antibody comprises an anti-human IgA antibody. 
     
     
         12 . The kit of  claim 9 , further comprising a citrullinated protein or peptide. 
     
     
         13 . The kit of  claim 9 , wherein the anti-CarP antibody is specific for a carbamylated protein or peptides derived from fetal calf's serum (FCS). 
     
     
         14 . The method according to  claim 1 , further comprising determining a further factor as an arthritis classifier for the individual. 
     
     
         15 . The method according to  claim 14 , wherein the further factor comprises determining ACPA, rheumatoid factor, C-reactive protein, and/or erythrocyte sedimentation rate. 
     
     
         16 . The method according to  claim 1 , wherein the body fluid is a serum sample or a synovial fluid sample. 
     
     
         17 . The method according to  claim 1 , wherein the anti-CarP and/or anti-Ca-Fib antibody is of Ig-subtype IgA or of the Ig-subtype IgG. 
     
     
         18 . The method according to  claim 17 , wherein the method further comprises determining whether a sample comprising a body fluid of the individual comprises an Anti-Citrullinated Protein Antibody (ACPA). 
     
     
         19 . The method according to  claim 18 , for determining whether the individual is at risk of suffering from arthritis, and wherein the individual was not suffering from arthritis at the time the fluid sample was obtained. 
     
     
         20 . The method according to  claim 18 , wherein the arthritis comprises rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, osteoarthritis, polymyalgia rheumatica, ankylosing spondylitis, reactive arthritis, gout, pseudogout, autoimmune arthritis, systemic lupus erythematosus, polymyositis, fibromyalgia, Lyme disease, undifferentiated arthritis, non-rheumatoid arthritis, or spondyloarthropathy.