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

David Gibson, Ji Qiu, Eliseo Mendoza, Kristi Barker, Madeleine Rooney, Joshua LaBaer

    Research output: Contribution to journalArticle

    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 diseasespecific 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.
    LanguageEnglish
    PagesR77
    JournalArthritis Research and Therapy
    Volume14
    Issue number2
    Publication statusPublished - 1 Jun 2012

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    Protein Array Analysis
    Juvenile Arthritis
    Acids
    Antibodies
    Autoantibodies
    Joints
    Synovial Fluid
    Proteome
    Reproducibility of Results
    Nucleic Acids
    Autoimmune Diseases
    Cluster Analysis
    Chronic Disease
    Cohort Studies
    Inflammation

    Cite this

    Gibson, David ; Qiu, Ji ; Mendoza, Eliseo ; Barker, Kristi ; Rooney, Madeleine ; LaBaer, Joshua. / Circulating and synovial antibody profiling of juvenile arthritis patients bynucleic acid programmable protein arrays. In: Arthritis Research and Therapy. 2012 ; Vol. 14, No. 2. pp. R77.
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    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 diseasespecific 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.",
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    Circulating and synovial antibody profiling of juvenile arthritis patients bynucleic acid programmable protein arrays. / Gibson, David; Qiu, Ji; Mendoza, Eliseo; Barker, Kristi; Rooney, Madeleine; LaBaer, Joshua.

    In: Arthritis Research and Therapy, Vol. 14, No. 2, 01.06.2012, p. R77.

    Research output: Contribution to journalArticle

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    AU - Qiu, Ji

    AU - Mendoza, Eliseo

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    AU - Rooney, Madeleine

    AU - LaBaer, Joshua

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