Abstract
IntroductionJuvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients.MethodsA pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs.ResultsQuantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis.ConclusionThe NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.
Highlights
Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children
rheumatoid factor (RF) was detected in only one patient (Patient P2), whereas antinuclear antigen (ANA) antibodies were present in four patients (Patients O1, O2, E1 and P4)
Intra-slide precision and inter-sample correlation In total, 768 antigen nucleic acid programmable protein array (NAPPA) were probed with plasma, synovial fluid, and the dilution buffer (Figure 1A and 1B)
Summary
Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. Juvenile idiopathic arthritis (JIA) is an autoimmune disease and the second most common disease of childhood after diabetes, affecting approximately one in every 1,000 children [1]. Genetic associations between JIA subtypes and HLA or non-HLA molecules are known to be related to immune response and associated with other autoimmune diseases [5,6]. Autoimmune phenomena such as autoreactive T cells and autoantibodies can be detected readily in most JIA subgroups [7,8,9]. Autoantibody tests for anti-cyclic citrullinated antibody, rheumatoid factor (RF) and antinuclear antigen (ANA) status have been adopted into clinical practice, and their role in diagnosis is well established in adult autoimmune diseases [10]
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