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Open Access Research article

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays

David S Gibson12*, Ji Qiu3, Eliseo A Mendoza3, Kristi Barker3, Madeleine E Rooney1 and Joshua LaBaer3

Author Affiliations

1 Arthritis Research Group, Centre for Infection and Immunity, Health Science Building, Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK

2 Division of Endocrinology, Metabolism and Diabetes, School of Medicine, University of Colorado Denver, 12800 E. 19th Avenue, Aurora, CO 80045, USA

3 Center for Personalized Diagnostics, Arizona State University, 1001 S. McAllister Avenue, Tempe, AZ 85287-6401, USA

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Arthritis Research & Therapy 2012, 14:R77  doi:10.1186/ar3800

Published: 17 April 2012

Abstract

Introduction

Juvenile 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.

Methods

A 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.

Results

Quantitative 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.

Conclusion

The 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.