A new antigenic epitope localized within human kappa light chains specificfor rheumatoid arthritis and systemic lupus erythematosus

Human B cell hybridomas were established to define new autoantigens of impo rtance for autoimmune diseases such as rheumatoid arthritis (RA). One lgG1, lambda monoclonal antibody (FKN-E12), was derived from synovial B lymphocy tes of a patient with sero-negative RA. The purified Ig was used to select specifically binding peptides from a random peptide phage display library. Only one epitope with the heptamer sequence HLTFGPG was detected and named RASFp1. Very similar and partly identical sequences are found in the variab le region of lg kappa light chains in position 96-101, at the junction of f ramework 2 and the J-region. The antibody FKN-E12 was shown to detect the e pitope RASFp1 also on human lgG kappa chains, but only in a specific confor mation. The aim of the present study was to analyse human sera from patient s with autoimmune diseases, non-autoimmune inflammatory diseases and health y blood donors for the presence of lgG-binding to RASFp1. For this purpose a 15-mer-peptide was synthesized containing RASFp1 within Vk-derived flanki ng regions, and an ELISA assay established. Sera of 142 individuals were st udied. Only <5% of the control sera including sera from patients with non-a utoimmune inflammations were positive. In contrast, 45% of sera from patien ts with RA or SLE contained RASFp1-binding antibodies. Within the 40 RA ser a analysed so far, rheumatoid factors and RASFp1-binding antibodies have sh own no correlation with each other. (C) 1999 Academic Press.