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14-3-3η Protein as a Potential Biomarker in Juvenile Idiopathic Arthritis
Austin Dalrymple1, Paul Tuttle1, Lance Feller1
1Division of Adult & Pediatric Rheumatology, Saint Louis University School of Medicine & SSM Health Cardinal Glennon Children's Hospital, Saint Louis, MO 63104, USA.
Insights
The 14-3-3 protein shows potential as a novel biomarker for juvenile idiopathic arthritis (JIA), especially in rheumatoid factor-negative polyarticular JIA cases. Elevated levels were observed in JIA patients compared to controls.
Area of Science:
- Immunology
- Pediatric Rheumatology
- Biomarker Discovery
Background:
- Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease affecting children.
- Current biomarkers for JIA lack specificity and sensitivity, necessitating the search for new diagnostic tools.
- The 14-3-3 protein family has been implicated in various cellular processes relevant to inflammation and autoimmunity.
Purpose of the Study:
- To evaluate the 14-3-3 protein (eta) as a potential biomarker in patients with JIA.
- To compare 14-3-3 protein levels in JIA patients with disease and healthy controls.
- To assess the clinical utility of 14-3-3 protein as a diagnostic marker for JIA subtypes.
Main Methods:
- A case-control study involving over 200 patients with JIA, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and healthy pediatric controls.
- Archival specimens collected between 1990 and 2011 were analyzed for 14-3-3 protein levels.
- Statistical analyses included Fisher's exact tests, odds ratios, and confidence intervals, comparing 14-3-3 positivity (≥0.2 ng/mL) with standard JIA markers (CBC, ESR, CRP, RF, anti-CCP, ANA).
Main Results:
- 14-3-3 protein positivity was detected in all JIA subtypes, with the highest rates in rheumatoid factor-positive (RF-pos) polyarticular JIA.
- Elevated 14-3-3 levels (≥0.5 ng/mL) were most frequent in RF-positive and RF-negative (RF-neg) polyarticular JIA patients.
- Approximately 30% of both RF-pos and RF-neg polyarticular JIA patients showed significant 14-3-3 levels.
- Some JIA patients positive for 14-3-3 later developed RF and anti-cyclic citrullinated peptide (anti-CCP) antibodies.
Conclusions:
- The 14-3-3 protein demonstrates potential as a novel biomarker for polyarticular JIA.
- Its utility may be particularly significant in identifying and monitoring RF-neg polyarticular JIA.
- Further research is warranted to establish 14-3-3 protein's role in JIA pathogenesis and clinical management.
Abstract:
The 14-3-3 (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 14-3-3 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. 14-3-3 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. 14-3-3 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 14-3-3 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 14-3-3 positivity developed RF and anti-CCP positivity later in their disease. Significant levels of 14-3-3 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.
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