Background/Purpose: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease. Currently, diagnosis is based on clinical assessment defined by the International League of Associations for Rheumatology criteria. Disease specific laboratory biomarkers are limited to rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies, which are associated with a poor JIA prognosis. The biomarker 14-3-3η (eta) is highly sensitive and specific for rheumatoid arthritis (RA) in adults. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of RF and CCP in adult RA and 14-3-3η level is associated with a more severe RA phenotype [1,2]. The objective of this study was to evaluate the prevalence and clinical significance of serum 14-3-3η in children with JIA.

Methods: One hundred patients from the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were divided into four groups: 31 with polyarticular JIA RF+ (PJIA RF+), 32 PJIA RF-, 25 oligoarticular JIA (OJIA), and 12 with psoriatic arthritis (PsA). OJIA patients served as a control group. RF, CCP, and 14-3-3η were measured via immunoturbidimetry, immunoassay, and ELISA, respectively. Based on adult onset RA, a 14-3-3η serum level of >0.2ng/mL was considered positive. Association of PJIA with 14-3-3η positivity was performed by Fisher’s exact test. Disease activity was assessed by Juvenile Arthritis Disease Activity Score-71 (JADAS-71), and correlation of 14-3-3η positivity with disease activity and with RF/CCP positivity by the Mantel-Haenszel statistics.

Results: RF, CCP, and 14-3-3η data are summarized in Table 1. Twenty eight patients had a positive 14-3-3η. Eight were single positive for 14-3-3η, 20 were positive for 14-3-3η and RF or CCP, and 15 were positive for all 3 markers. There was positive correlation between 14-3-3η and RF and CCP positivities (p=0.00001), but there was no correlation between presence and titer of 14-3-3η compared to JADAS-71 or age of onset.

Conclusion: All patient groups tested had levels of 14-3-3η above baseline. PJIA RF+ patients had the highest prevalence of 14-3-3η compared to all other groups. There was positive correlation between 14-3-3η and positive RF and CCP, but none with disease activity. Of note, 14-3-3η was positive in other forms of JIA, including OJIA where 25% of patients were positive. 14-3-3η may be a useful biomarker in diagnosis, prognosis and monitoring therapeutic response of children with PJIA RF+. However, its role in other forms of JIA remains to be determined.

References:

1. Maksymowych WP, Marotta A. 14-3-3η: a novel biomarker platform for rheumatoid arthritis. Clin Exp Rheumatol. 2014:32(suppl):S-35-9.

2. Maksymowych WP, Naides SJ, Bykerk V, et al. Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41:2104-2113.

Table 1: Prevalence of 14-3-3η, RF and CCP Across Patient Groups

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-of-serum-14-3-3%ce%b7-in-juvenile-idiopathic-arthritis/