Prevalence and significance of serum 14–3-3η in juvenile idiopathic arthritis

Abstract

Background Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14–3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14–3-3η in different types of JIA. Methods JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14–3-3η were measured for all patients. 14–3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Results Elevated 14–3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14–3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14–3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14–3-3η. The highest prevalence of 14–3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14–3-3η was not significantly associated with disease activity or age at diagnosis. Conclusion Serum 14–3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14–3-3η does not appear to correlate with disease activity in JIA.

Serum 14-3-3 ETA levels in ankylosing spondylitis with pure axial involvement: Could it be a potential biomarker to assess disease activity?

“…It is a well-known fact that the eta protein contributes to the inflammation seen in RA (25). However, no correlation has been shown between serum eta levels and disease activity in juvenile inflammatory arthritis (JIA) and systemic lupus erythematosus, which are among other rheumatic diseases (10,15).…”

“…These proteins are involved in the regulation of intracellular activities by binding to various intracellular proteins (8). The 14-3-3η protein is involved in a variety of biological processes, including cell proliferation, differentiation, and apoptosis, which are involved in inflammation (9,10). The 14-3-3η protein is encoded by genes located on chromosomes, and more than 200 proteins are known to interact with eta proteins (11).…”

“…MMPs are associated with structural damage in RA and are potential markers of progressive joint damage and disease activity (14). Subsequent studies have investigated the relationship between various rheumatic diseases and serum eta levels (10,12,15).…”