Identification of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein A2

Rheumatoid arthritis (ra) is a chronic autoimmune disorder,characterized by progressive joint destruction and disability. classical autoantibodies of ra are rheumatoid factors and citrulline antibodies. patients positive for these autoantibodies are usually associated with a progressive disease course. a subgroup of ra patients does not express citrulline antibodies,instead are approximately 35% of these anti-citrulline-negative patients reported to express autoantibodies to the heterogeneous nucleoriboprotein a2,a ribonucleoprotein involved in rna transport and processing also referred to as ra33. in the absence of citrulline antibodies,ra33 antibodies have been suggested to be associated with a milder disease course. in this study we screened the reactivity of a monoclonal antibody to ra33-derived peptides by modified enzyme-linked immunosorbent assays (elisa). terminally truncated resin-bound peptides were applied for determination of the functional epitope necessary for antibody recognition. in addition,screening of substituted peptides by modified elisa identified amino acids necessary for antibody reactivity. a potential epitope was identified in the region 71-79 (phsidgrvv),where the amino acids ser,ile and asp were found to be essential for antibody reactivity. these amino acids were found to contribute to the antibody-antigen interface through side-chain interactions,possibly in combination with a positively charged amino acid in position 77. moreover,the amino acids in the n-terminal end (pro and his) were found to contribute to the interface through backbone contributions. no notable reactivity was found with ra-positive patient sera,thus screening of ra33 antibodies does not seem to be a supplementary for the diagnosis of ra. © 2014 bentham science publishers.