ABSTRACT
The 14-3-3η (eta) protein was evaluated as a biomarker in a cohort of patients with juvenile idiopathic arthritis (JIA), as well as disease- and healthy-controls, to determine its potential clinical utility. In this case-control study, levels of 14-3-3η protein were evaluated in archival specimens from patients with JIA, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), as well as healthy pediatric controls. Just over 200 patients were evaluated, using specimens banked between 1990 and 2011. Comparisons were made to complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-nuclear antibody (ANA) positivity. 14-3-3η at levels 0.2 ng/mL or higher was considered positive. Fisher's exact tests, odds ratios, 95% confidence intervals, and p-values were reported. 14-3-3η positivity was seen in all included JIA subtypes. The rate of positivity was the highest in RF-positive (pos) polyarticular JIA. In the disease and healthy controls, lower rates of positivity were observed. The frequency of 14-3-3η positivity among RF-positive and RF-negative (neg) polyarticular JIA patients, especially at values ≥0.5 ng/mL (associated with poor outcomes in adults), was also highest. Several JIA patients with 14-3-3η positivity developed RF and anti-CCP positivity later in their disease. Significant levels of 14-3-3η can be found in approximately 30% of RF-pos and RF-neg patients with polyarticular JIA. This protein may represent a new biomarker for polyarticular JIA, particularly RF-neg polyarticular JIA.
ABSTRACT
OBJECTIVES: Our objective was to evaluate sera from juvenile idiopathic arthritis (JIA) patients to investigate the presence of isotypes (IgA, IgG, IgM) of anti-citrullinated fibrinogen and anti-α-enolase antibodies and their association with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody isotypes. METHODS: Sera were obtained from 89 JIA patients and were measured for isotypes (IgA, IgM) of anti-citrullinated and native fibrinogen and anti-α-enolase antibodies by enzyme-linked immunosorbent assay. Results were compared to anti-CCP antibody isotypes and RF isotypes, in addition to previously measured IgG anti-citrullinated fibrinogen and α-enolase antibodies. RESULTS: IgA anti-citrullinated fibrinogen antibodies were positive in 20 JIA patients and IgM in 11 JIA patients. Two IgM RF-positive polyarthritis patients were positive for all 3 isotypes of anti-citrullinated fibrinogen antibodies. IgA anti-citrullinated α-enolase antibodies were positive in 7 JIA patients and IgM in 9 JIA patients. IgA and IgG anti-citrullinated fibrinogen antibodies were commonly found in JIA patients positive for IgG anti-CCP antibodies and IgM RF. IgG anti-CCP antibodies and IgM RF levels were significantly higher in JIA patients with 3 or more anti-citrullinated autoantibody isotypes present. CONCLUSIONS: We have shown that isotypes of anti-citrullinated fibrinogen and α-enolase can be found in the serum of children with JIA of all onset types. Citrullinated autoantibody isotype diversity may indicate a more severe disease course in JIA patients.
