ENHANCED EXPRESSION OF IMMUNOGLOBULIN-KAPPA LIGHT-CHAINS WITH UNUSUALLY LONG CDR3 REGIONS IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. Our previous sequence analysis of immunoglobulin Ic light c hains revealed that some patients with rheumatoid arthritis (RA) expre ssed repertoires enriched for transcripts containing unusually long CD R3 lengths of 11 amino acid codons. This was due, in part, to N region addition at the V kappa-J kappa joins. In this study, we analyzed a l arger number of individuals to determine how often enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in synovial lym phocytes and peripheral blood lymphocytes (PBL) of individuals with RA . Methods. To measure length variability of kappa chain CDR3 regions, we performed a 2 stage polymerase chain reaction amplification and pol yacrylamide gel electrophoresis. We sampled PBL and synovial lymphocyt es of 9 patients with longstanding RA, and used PBL of 9 age and sex m atched healthy individuals as controls. Results. In PBL of healthy ind ividuals, there was low level but consistent expression of kappa chain s containing CDR3 with 11 amino acids. In patients, there was enhanced expression of Ic chains containing CDR3 with 11 amino acids compared to healthy individuals. This enhanced expression of kappa chains conta ining CDR3 of 11 amino acids was more pronounced in synovial lymphocyt es compared to PBL of the same patients. Conclusion. These findings su ggest that there is antigenic selection of B cells bearing antibodies with unusually long kappa light chain CDR3 in RA.