Background/Purpose:

IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as an important indicator of destructive disease in juvenile idiopathic arthritis (JIA), as is the case in rheumatoid arthritis (RA). We evaluated sera from patients with three subtypes of JIA, in addition to RA patients and healthy individuals to investigate the significance of anti-CCP titers in relation to disease severity.

Methods:

Sera from 90 JIA patients were collected, including 30 IgM RF-positive polyarthritis, 30 IgM RF-negative polyarthritis, and 30 oligoarthritis. Sera were collected from 30 patients with RA and 30 healthy individuals. All sera were measured for IgG anti-CCP antibodies and IgM RF by ELISA. IgG anti-CCP antibody serum levels more than three times the cut-off (>60 Units) were considered high titer (HT) antibody levels. Patient records were evaluated for clinical and laboratory associations, including joint damage.

Results:

Fifteen IgM RF-positive polyarthritis patients had HT IgG anti-CCP antibodies, 5 had low titer (LT) anti-CCP antibodies, and 10 were considered negative. Two IgM RF-negative polyarthritis were positive for IgG anti-CCP antibodies, one with HT and one with LT. None of the oligoarthritis patients were positive for IgG anti-CCP antibodies, while 2 healthy children had LT IgG anti-CCP antibodies. Eighteen RA patients had HT IgG anti-CCP antibodies, one LT, and 11 were considered negative. IgM RF-positive polyarthritis patients demonstrated significantly elevated levels of IgG anti-CCP antibodies (85±80 Units) compared to IgM RF-negative polyarthritis (14±38 Units), oligoarthritis (5±5 Units), and healthy children (6±7 Units) (p<0.001). When IgM RF-positive polyarthritis levels were compared with levels in RA patients (102±85 Units), the difference was not significant (p=0.436). Nine of 16 (56.3%) JIA patients with HT IgG anti-CCP antibodies and 2/6 (33.3%) with LT IgG anti-CCP antibodies had joint damage. JIA patients with joint damage had significantly higher levels of IgG anti-CCP antibodies (83±84 Units) compared to those with no joint damage (23±49 Units) (p=0.008). Thirteen of 18 (72.2%) RA patients with HT, 1 LT, and 6/11 (54.5%) negative for IgG anti-CCP antibodies had joint damage. The difference in IgG anti-CCP antibody levels did not differ significantly in RA patients with or without joint damage (p=0.17). IgM RF levels were also significantly higher in JIA patients with joint damage (54±56 Units) compared to those with no joint damage (20±30 Units; p=0.026). Regression analysis showed that HT anti-CCP antibodies were the strongest independent determinant of joint damage in JIA (OR 8.13 [95% CI: 2.37-27.84], p=0.001). 

Conclusion:

IgM RF-positive polyarticular JIA and adult RA patients demonstrated similar mean levels of IgG anti-CCP antibodies, both greater than the HT cut-off of >60 Units. HT anti-CCP antibodies were strongly associated with joint damage in JIA. Measurement of IgG anti-CCP antibody serum levels was found to be useful in identifying JIA patients with destructive disease and would be useful in management of JIA, particularly patients with IgM RF-positive polyarthritis and overall in JIA patients exhibiting HTs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-titer-igg-anti-cyclic-citrullinated-peptide-antibodies-are-associated-with-joint-destruction-in-juvenile-idiopathic-arthritis-patients/