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. Elevated serum levels of 14-3-3η (eta) biomarker have improved the diagnostic sensitivity of RF and CCP in adult RA and elevated 14-3-3η 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 fifty two patients from the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were divided into five groups: 39 with polyarticular JIA RF+ (PJIA RF+), 39 PJIA RF-, 36 oligoarticular JIA (OJIA), 20 with psoriatic arthritis (PsA) and 18 with enthesitis-related arthritis (ERA). 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 JIA with 14-3-3η positivity was performed by Fisher’s exact test. Disease activity was assessed by Juvenile Arthritis Disease Activity Score-10/71 (JADAS-10/71).

Results: RF, CCP, and 14-3-3η data are summarized in Table 1. Thirty five (23%) patients had a positive 14-3-3η. Twelve (8%) were single positive for 14-3-3η, 23 (15%) were positive for 14-3-3η and RF and/or CCP, and 17 (11%) were positive for all 3 markers. There was a positive correlation between 14-3-3η and PJIA RF+ vs. OJIA (p-value = 0.029) and PJIA RF+ vs. PsA (p-value = 0.012) and, but there was no correlation between presence and titer of 14-3-3η compared to JADAS-10/71.

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. Of note, 14-3-3η was positive in other forms of JIA, especially OJIA where 22% of patients were positive. There was a positive correlation between 14-3-3η and positive RF and CCP, but none with disease activity. 14-3-3η might be a useful biomarker in the diagnosis, prognosis and in 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 14-3-3h, RF and CCP Across Patient Groups Compared to OligoJIA

*Indicates significant findings.

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