Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Anti-CCP Antibodies Identify a Subset of RF-Negative Juvenile Idiopathic Arthritis.
Tebo2, Anne E., Jaskowski1, Troy D., Davis1, K. Wayne, Vigus6, April, Clifford4, Bronte, Zeft5, Andrew S., McNally5, Bernadette
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children. One subtype of JIA, characterized by rheumatoid factor (RF) positive polyarthritis, phenotypically resembles rheumatoid arthritis (RA) in adults. Recent studies have demonstrated anti-citrullinated protein/peptide antibodies (ACPA), have high specifity for RA. Furthermore most known genetic associations with RA are confined to autoantibody positive RA (ACPA and/or RF). Prior investigations of the prevalence of ACPA in children have mostly been in small cohorts of children with JIA, with very few cases of RF-positive polyarticular JIA included. We sought to investigate the prevalence of ACPA in a large well-characterized cohort of JIA and investigate the relationship between RF and ACPA.
Cases were 334 children with JIA, 30 of whom had RF+ polyarticular JIA. The mean age of onset in the JIA cohort was 6.7 years. Controls were 50 healthy children with a mean age of 11.5 at the time of blood draw. Sera from all JIA patients and healthy controls were investigated at a single time point for anti-cyclic citrullinated peptide (anti-CCP) IgG by ELISA (INOVA Diagnostics, San Diego, CA), RF IgM, IgA and IgG (Theratest, Lombard, IL), anti-RA33 ELISA (IMTEC, Wiesbaden, Germany), antinuclear antibodies (ANA) screened by ELISA (BioRad, USA) and positives confirmed by IFA on HEp2 cells. Comparisons between cases and controls were made using Chi-square or Fisher exact tests for categorical variable and T-tests for continuous variables.
The prevalence of RF was 8% among controls, and 12% among cases, (not statistically significant). However the mean titer of RF was higher among positive cases. ACPA were detected in one control and 48 cases (2% vs. 14.3 %; OR 8.2, p <0.01). Of particular interest were 23 children (7%) who had a positive ACPA and were negative for RF (IgM, IgG or IgA). These children had a significantly earlier age of onset than those children who had both RF and ACPA (4.6 years vs. 12.1 years, p <0.00001 by T-test), included more males (8/23 vs. 2/30, p <0.01), and included children with polyarticular (n = 6) as well as oligoarticular onset (n = 10). High resolution HLA-DRB1 genotyping indicated that they had fewer shared epitope alleles compared to those with ACPA and RF, who resembled adults with RA. Twenty-five JIA cases had both RF and ACPA, and generally had higher titers of ACPA than those with only ACPA. Among children classified as having RF+ polyarticular JIA per ILAR criteria, 73% were positive for ACPA. Notably, two children with ACPA and RF had oligoarticular onset and were classified as "undifferentiated JIA" per the ILAR criteria. ANA was positive in 6% of controls and 26% of cases by IFA (OR 5.6, p <0.01). RA-33 antibodies were observed in 6% of controls, and 6% of cases (not significantly different).
Using the largest cohort investigated to date for ACPA, we have demonstrated that anti-CCP antibodies are detectable in 15% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. If validated in other large JIA cohorts, ACPA testing should be included in the classification of JIA.
To cite this abstract, please use the following information:
Tebo, Anne E., Jaskowski, Troy D., Davis, K. Wayne, Vigus, April, Clifford, Bronte, Zeft, Andrew S., et al; Anti-CCP Antibodies Identify a Subset of RF-Negative Juvenile Idiopathic Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :245