Antibodies to citrullinated peptides in patients with juvenile idiopathic arthritis and rheumatoid arthritis: Shared expression of the inherently autoreactive 9G4 idiotype

Objective Antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis (RA) can express the inherently autoreactive gene, VH4-34, as detected using the rat monoclonal antibody, 9G4. Patients with the polyarticular sub-type of juvenile idiopathic arthritis (pJIA) share some but not all features of RA in adults. The aim of this study was to profile rheumatoid factor (RF), anti-CCP and 9G4-CCP serology of a large JIA cohort and compare to a cohort of adult RA patients. Methods Serum from 88 pJIA, 29 enthesitis-related arthritis (ERA), 38 extended oligoarthritis (EOA), 31 adolescent controls, 35 RA and 30 adult controls were tested for RF, IgG, IgA and IgM anti-CCP and 9G4+CCP by ELISA. Serum total 9G4+IgM was also measured. Results Of 65/88 pJIA(RF-ve) patients, 4 (4.6%) were IgG anti-CCP positive. In sera from pJIA(RF+ve) 20/23 (87.0%), RA 30/35 (85.7%) and one EOA patient contained IgG anti-CCP. IgA- and IgM anti-CCP levels were lower in the adolescent group (p<0.01). 9G4-CCP were higher in pJIA RF+ve vs RF-ve (p<0.0001). Median levels of 9G4-CCP in pJIA(RF+ve) and RA did not differ. 9G4 on serum total IgM was greater in pJIA(RF+ve) patients compared with adolescent groups (p<0.01), but similar to adult RA(RF+ve). Conclusion In healthy individuals, 9G4+B cells comprise 5-10% of peripheral blood pool but serum immunoglobulins utilising VH4-34 are disproportionately low. The idiotope recognised by 9G4 was detected on anti-CCP antibodies in >80% pJIA(RF+ve) patients. VH4-34 usage by anti-CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes. This article is protected by copyright. All rights reserved.