A New Antigenic Epitope Localized Within Human κLight Chains Specific for Rheumatoid Arthritis and Systemic Lupus Erythematosus

Abstract

Human B cell hybridomas were established to define new autoantigens of importance for autoimmune diseases such as rheumatoid arthritis (RA). One lgG1, λ monoclonal antibody (FKN-E12), was derived from synovial B lymphocytes of a patient with sero-negative RA. The purified lg 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 variable region of lg κ light chains in position 96–101, at the junction of framework 2 and the J-region. The antibody FKN-E12 was shown to detect the epitope RASFp1 also on human lgG κ chains, but only in a specific conformation. The aim of the present study was to analyse human sera from patients with autoimmune diseases, non-autoimmune inflammatory diseases and healthy blood donors for the presence of lgG binding to RASFp1. For this purpose a 15-mer-peptide was synthesized containing RASFp1 within Vk-derived flanking regions, and an ELISA assay established. Sera of 142 individuals were studied. Only <5% of the control sera including sera from patients with non-autoimmune inflammations were positive. In contrast, 45% of sera from patients with RA or SLE contained RASFp1-binding antibodies. Within the 40 RA sera analysed so far, rheumatoid factors and RASFp1-binding antibodies have shown no correlation with each other.