Enhanced expression of immunoglobulin kappa light chains with unusually long CDR3 regions in patients with rheumatoid arthritis.

Overview

OBJECTIVE: Our previous sequence analysis of immunoglobulin kappa light chains revealed that some patients with rheumatoid arthritis (RA) expressed repertoires enriched for transcripts containing unusually long CDR3 lengths of 11 amino acid codons. This was due, in part, to N region addition at the Vkappa-Jkappa joins. In this study, we analyzed a larger number of individuals to determine how often enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in synovial lymphocytes 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 polyacrylamide gel electrophoresis. We sampled PBL and synovial lymphocytes of 9 patients with longstanding RA, and used PBL of 9 age and sex matched healthy individuals as controls. RESULTS: In PBL of healthy individuals, there was low level but consistent expression of kappa chains containing CDR3 with 11 amino acids. In patients, there was enhanced expression of kappa chains containing CDR3 with 11 amino acids compared to healthy individuals. This enhanced expression of kappa chains containing CDR3 of 11 amino acids was more pronounced in synovial lymphocytes compared to PBL of the same patients. CONCLUSION: These findings suggest that there is antigenic selection of B cells bearing antibodies with unusually long kappa light chain CDR3 in RA.