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Published on: February 8, 2019
Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis
Anne E Tebo1, Troy Jaskowski, K Wayne Davis
1Department of Pediatrics and Human Genetics, Emory University School of Medicine, 2015 Uppergate Drive NE, Atlanta, GA, 30322, USA. sprahal@emory.edu.
Insights
Anti-citrullinated protein/peptide antibodies (ACPA) are found in 14% of children with juvenile idiopathic arthritis (JIA). ACPA-positive, rheumatoid factor-negative JIA may represent a distinct subgroup requiring specific classification.
Area of Science:
- Pediatric Rheumatology
- Immunology
- Autoimmunity
Background:
- Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific for rheumatoid arthritis (RA).
- Juvenile idiopathic arthritis (JIA) can phenotypically mimic RA, with some patients testing positive for rheumatoid factor (RF).
- The prevalence and significance of ACPA in JIA remain under investigation.
Purpose of the Study:
- To determine the prevalence of ACPA in a JIA cohort.
- To examine the relationship between ACPA, RF, and other serologic markers in JIA.
- To explore potential distinct JIA subsets based on ACPA and RF status.
Main Methods:
- Sera from 334 children with JIA and 50 healthy controls were analyzed using ELISA.
- Tests included anti-cyclic citrullinated peptide (anti-CCP) IgG, RF (IgM, IgA, IgG), anti-RA33 IgG, and antinuclear antibodies (ANA).
- Statistical comparisons utilized Chi-square, Fisher exact tests, and T-tests.
Main Results:
- ACPA prevalence was 14.3% in JIA cases versus 2% in controls (OR 8.2, p <0.01).
- RF prevalence was 12% in JIA cases and 8% in controls.
- ACPA-positive, RF-negative JIA patients (n=23) had earlier onset (4.6 years) and fewer HLA-DRB1 alleles than RF/ACPA-positive patients (n=25).
Conclusions:
- ACPA are detectable in a significant subset (14%) of children with JIA.
- A frequent subgroup of JIA patients presents with ACPA but without RF, suggesting a distinct clinical entity.
- ACPA testing may be valuable for JIA classification and understanding disease subsets.
Background:
Anti-citrullinated protein/peptide antibodies (ACPA), have high specificity for rheumatoid arthritis (RA). Some children with juvenile idiopathic arthritis (JIA), phenotypically resemble RA and test positive for rheumatoid factor (RF) a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort.
Methods:
Cases were 334 children with JIA, 30 of whom had RF + polyarticular JIA. Sera from all cases and 50 healthy pediatric controls were investigated by ELISA at a single time point for anti-cyclic citrullinated peptide (anti-CCP) IgG, RF IgM, IgA and IgG, anti-RA33 IgG, and antinuclear antibodies (ANA). Comparisons between cases and controls were made using Chi-square or Fisher exact tests and T-tests.
Results:
The prevalence of RF was 8% among controls, and 12% among cases (ns). The prevalence of ACPA was 2% in controls and 14.3% in cases (OR 8.2, p <0.01). Children who were ACPA-positive and RF-negative (n = 23) had a significantly earlier onset-age (4.6 years vs. 12.1 years, p <0.00001) and had fewer HLA-DRB1 shared epitope alleles than those positive for both RF and ACPA (n = 25). Prevalence of anti-RA33 was not different between cases and controls.
Conclusions:
ACPAs are detectable in 14% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. ACPA testing should be included in the classification of JIA.
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