Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis.

Nadége Nziza,Christian Jorgensen,Marion Delpont,Alain Mangé,Aurélia Carbasse,Maïlys Cren,Hamouda Abassi,Florence Apparailly,Eric Jeziorski,Hugues Chevassus,Eric Schordan,Perrine Mahe,Pauline Joly-Monrigal,Isabelle Duroux-Richard

doi:10.3390/cells8121521

Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatism in childhood; microRNAs (miRNAs) have been proposed as diagnostic biomarkers. Although joints are the primary targets for JIA, a synovial fluid-based miRNA signature has never been studied. We aim to identify miRNA biomarkers in JIA by comparing synovial fluid and serum samples from children with JIA and K. kingae septic arthritis (SA). With next-generation high-throughput sequencing, we measured the absolute levels of 2083 miRNAs in synovial fluid and serum from an exploratory cohort of children and validated differentially expressed miRNAs in a replication study by using RT-qPCR. We identified a 19-miRNA signature only in synovial fluid samples that was significantly deregulated, with at least 2-fold change in expression, in JIA versus SA (p < 0.01). The combination of miR-6764-5p, miR-155, and miR-146a-5p expression in synovial fluid yielded an area under the receiver operating characteristic curve of 1 (95% CI 0.978 to 1), thereby perfectly differentiating JIA from SA in children. We propose, for the first time, a synovial fluid-specific miRNA signature for JIA and associated signaling pathways that may indicate potential biomarkers to assist in the classification and differential diagnosis of JIA and help in understanding JIA pathogenesis.

Highlights

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory disease in childhood and is characterized by arthritis and systemic features
The present study aims to identify miRNA-based biomarkers to better characterize JIA diseases by using three novel tracks: (1) next-generation high-throughput screening; (2) synovial fluid, the main tissue involved in JIA diseases; and (3) children with septic arthritis (SA) as controls because of the inability to collect synovial fluid from joints of healthy children and because it is the most frequent aetiology in children hospitalized for arthritis, just before JIA, albeit involving different treatment and prognoses
To identify miRNAs differentially expressed in JIA versus SA, we analyzed the miRNome in SE

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory disease in childhood and is characterized by arthritis and systemic features. JIA represents a heterogeneous group of inflammatory arthropathies, whose classification has been recently revised by the International League of Associations for Rheumatology (ILAR) [1]. Childhood and adult rheumatic diseases share some similarities, they have fundamental differences such as clinical features, prognosis, and pathophysiology, which are not yet well understood. Rheumatoid arthritis (RA) is clearly an autoimmune disease strongly associated with autoantibodies against citrullinated peptides and IgG (rheumatoid factor [RF]), which are used for diagnosis and are involved in the disease pathophysiology [4]. The new ILAR classification considers that only systemic JIA, RF-positive JIA, and enthesitis/spondylitis-related JIA are the juvenile counterparts of diseases observed in adults, with other JIA diseases occurring only in children

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