Antifilaggrin antibodies comprise a heterogeneous population of antibodies directed to citrullinated proteins.
Recent studies have shown that their production is highly specific for rheumatoid arthritis (RA) and the initial antigenic trigger for these autoantibodies can be localised to the inflammed synovial tissue.
The aim of our study was to compare the reactivity and specificity of antibodies in sera and synovial fluids towards citrullinated epitopes. Peptide sequence corresponding to human profilaggrin (amino acid residues 306–324) and sequences with citrulline substitution at different positions were synthetised by mutipin peptide synthesis on solid supports. Shortened versions of the peptide were also produced by removal of amino acid residues from its N and C terminals. Completely citrullinated variant of the 14-mer peptide was also prepared. Peptide with no citrulline replacement was used as a control antigen. We found significant differences in the sensitivity for RA of 19 individual peptides tested (from 5% to 68%), reflecting previous results that the surrounding amino acids play an important role in creation of an autoantigenic epitope. Further, we tested the reactivities of paired serum and synovial fluids and found very similar peptide recognition patterns in serum and synovial IgG from the same individuals. Studies on larger number of samples are in progress to evaluate the results statistically that may support further evidence of the synovial origin of antifilaggrin autoantibodies.
This work was supported by the Hungarian grant OTKA T037876.