Session Title: Pediatric Rheumatology – Pathogenesis and Genetics - Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid factor (RF) positive polyarticular JIA (RF+ve pJIA) frequently progresses into adulthood with a clinical phenotype that ressembles rheumatoid arthritis (RA). Antibodies to cyclic citrullinated peptides (anti-CCP) have also been detected in a high proportion of sera from patients with RF+ve pJIA. We have previously described the use of an inherently autoreactive VH (variable heavy immunoglobulin chain) by anti-CCP in patients with early and also established adult RA . Immunoglobulins derived from this gene (VH4-34) can be tracked using the rat monoclonal antibody, 9G4. This study profiles RF, anti-CCP and 9G4-CCP serology of a large adolescent JIA cohort compared with that of adult patients with RA.
Methods: Serum from 88 poly-JIA, enthesitis-related arthritis (ERA;n=29), extended oligoarthritis (EOA;n= 38), 31 gender/age matched controls, 35 adult RA and 30 age-matched healthy controls (HC). IgG, IgA and IgM isotypes of anti-CCP was tested. Cut-offs for positivity were defined by manufacturer’s instructions or determined with reference to known positive standards and expressed as arbitrary units (AU). RF status was determined by in-house ELISA. 9G4 expression on antibodies binding to CCP-coated ELISA plates was as previously described. A capture ELISA was used to measure serum total 9G4-IgM. Mann-Whitney U was used to compare groups and linear regression for relationships between variables.
Results: Of 88 patients with polyJIA, 65 were RF-ve with 4 (6%) positive for IgG-CCP. In RF+ve pJIA and RF+ve adult RA groups, 20/23 (87%) and 30/35 (86%) sera contained IgG-CCP respectively. 1 patient (with EOA) in adolescent patient group had IgG-CCP. Levels of IgG-CCP were similar between RF+ve pJIA and RF+ve RA but both IgA- and IgM-CCP levels were significantly lower in the adolescent group (p<0.01 for both). Binding of 9G4 to anti-CCP antibodies was significantly higher in the RF+ve pJIA vs RhF-ve pJIA (Median 9.8 vs 1.2; p<0.0001). Similar median levels of 9G4-CCP were present in RF+ve pJIA and adult RF+ve RA (p=0.13). 9G4 expression on serum total IgM was significantly higher in RF+ve pJIA patients compared with adult healthy control and JIA disease control groups (EOA, ERA and RF-ve pJIA all p<0.01), but similar to that of adult RF+ve RA.
Conclusion: This study is the first to describe the inherently autoreactive idiotope recognised by 9G4 being detected on anti-CCP antibodies in RF+ve pJIA. Restriction in VH gene usage in both JIA and RA patient immune systems may bias their immunoglobulin repertoire and be instrumental in the elicitation of anti-CCP antibodies. IgG-anti-CCP response of RF+ve pJIA and adult RA patients were similar. However, significantly higher levels of IgA- and IgM-anti-CCPs were present in adult RA patients. Interestingly, we previously showed that in adult RA with onset of <1 year, percentage of samples positive for IgM- and IgA-CCP followed, rather than preceded positivity for IgG-anti-CCP. This suggests that the emergence of IgG-antibodies to a citrullinated proteins may arise early in the underlying pathogenic process with a sequence of events not shared with conventional antibody responses to pathogens. 1.Cambridge G et al: PloS one 2014, 9(9):e107513.
To cite this abstract in AMA style:Peckham H, Bourke L, Radziszewska A, Leandro MJ, Sen D, Cambridge G, Ioannou Y. Antibodies to Citrullinated Peptides in Patients with Juvenile Idiopathic Arthritis and Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/antibodies-to-citrullinated-peptides-in-patients-with-juvenile-idiopathic-arthritis-and-rheumatoid-arthritis-shared-expression-of-the-inherently-autoreactive-9g4-idiotype/. Accessed November 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-citrullinated-peptides-in-patients-with-juvenile-idiopathic-arthritis-and-rheumatoid-arthritis-shared-expression-of-the-inherently-autoreactive-9g4-idiotype/