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Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis and Patients With Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype
Author(s) -
Peckham Hannah,
Cambridge Geraldine,
Bourke Lauren,
Sen Debajit,
Radziszewska Anna,
Leandro Maria,
Ioannou Yiannis
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40117
Subject(s) - medicine , oligoarthritis , rheumatoid factor , arthritis , rheumatoid arthritis , immunology , antibody , serology , polyarthritis , idiotype , cohort , gastroenterology , monoclonal antibody
Objective Antibodies to cyclic citrullinated peptides (anti‐CCP) in rheumatoid arthritis (RA) can express the inherently autoreactive gene V H 4–34, detected using the rat monoclonal antibody 9G4. Patients with the polyarticular subtype of juvenile idiopathic arthritis (JIA) share some but not all of the features of adult patients with RA. This study was undertaken to compare serologic findings for rheumatoid factor (RF), anti‐CCP, and 9G4‐expressing anti‐CCP in a large JIA cohort with a cohort of adult RA patients. Methods Serum from 88 patients with polyarticular JIA, 29 patients with enthesitis‐related arthritis, 38 patients with extended oligoarthritis, 31 adolescent controls, 35 patients with RA, and 30 adult controls were tested for RF, for IgG, IgA, and IgM anti‐CCP, and for 9G4‐expressing anti‐CCP by enzyme‐linked immunosorbent assay. Total serum 9G4‐positive IgM was also measured. Results Of 65 patients with RF‐negative polyarticular JIA, 4 (6.2%) were IgG anti‐CCP positive. Sera from 20 of 23 patients with RF‐positive polyarticular JIA (87.0%), 24 of 35 patients with RA (68.6%), and 1 patient with extended oligoarthritis contained IgG anti‐CCP. IgA and IgM anti‐CCP levels were lower in the adolescent group ( P < 0.01). Levels of 9G4‐expressing anti‐CCP were higher in patients with RF‐positive polyarticular JIA than in those with RF‐negative polyarticular JIA ( P < 0.0001). Median levels of 9G4‐expressing anti‐CCP in patients with RF‐positive polyarticular JIA and those with RA did not differ. Expression of 9G4 on serum total IgM was greater in patients with RF‐positive polyarticular JIA than other adolescent groups ( P < 0.01), but similar to adult RF‐positive RA. Conclusion In healthy individuals, 9G4‐positive B cells comprise 5–10% of the peripheral blood pool but serum immunoglobulins utilizing V H 4–34 are disproportionately low. The idiotope recognized by 9G4 was detected on anti‐CCP antibodies in >80% of patients with RF‐positive polyarticular JIA. V H 4–34 usage by anti‐CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes.