JNK Pathway-Associated Phosphatase as a Serum Marker for Disease Activity and Treatment Outcome of Juvenile Idiopathic Arthritis.

Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by arthritis of unknown etiology. JNK pathway-associated phosphatase (JKAP) is reported to be a negative regulator of T-cell activation, but its clinical role in JIA is unknown. This study aimed to investigate the correlation of JKAP with disease activity and treatment response to a tumor necrosis factor (TNF) inhibitor, etanercept (ETN), in JIA patients. Totally, 104 JIA patients (6.9 ± 2.7 years old) and 100 age- and sex-matched healthy controls (HCs) (7.2 ± 2.4 years old) were enrolled, and their serum samples were collected for measuring JKAP by enzyme-linked immunoassay. In JIA patients, after 24-week ETN treatment, clinical response was assessed based on the American College of Rheumatology pediatric criteria (ACRpedi) 50 criteria. Results showed that JKAP levels were significantly lower in JIA patients compared with HCs, and of good value in differentiating JIA patients from HCs. Among JIA patients, higher JKAP levels were associated with lower disease activity indexes, including C-reactive protein, number of joints with active arthritis, physician's global assessment of disease activity, and the present history of disease-modifying antirheumatic drugs; higher baseline JKAP levels were correlated with worse ACRpedi 50 response to ETN at week 24, and was also an independent predictive factor for worse ACRpedi 50 response to ETN. Thus, it may be inappropriate to use ETN for JIA patients with higher JKAP levels. In conclusion, serum JKAP is a potential biomarker for JIA activity and treatment response to a TNF inhibitor.