Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort

D.S. Gibson, M.E. Rooney, M.E. Rosenkranz, R. Hirsch, C. Scaife, S. Pennington

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    Abstract

    Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. In a prior study, the synovial fluid (SF) proteome of an oligoarticular patient subgroup was compared to patients who show a spread of disease in the first year to involve new joints, the extended oligoarticular subgroup. Current laboratory tests are unable to flag those patients at a higher risk of disease spread to multiple joints, who could benefit form earlier therapy to prevent joint damage. This study investigated whether profiling of the SF proteome based a difference gel electrophoresis (DIGE) approach could differentiate between subgroups of this chronic disease.Methods:To construct a predictive model, SF samples from 22 JIA patients were analysed: 10 oligo-, 5 extended oligo- and 7 polyarticular disease. Samples from each patient were labeled with Cy dyes and subjected to protein separation by 2-DE. The predictive value of using a panel of SF proteins to stratify patients was tested on an independent pool of 28 JIA patients: 13 oligo-, 5 extended oligo- and 10 polyarticular disease. Protein spots of interest which over expressed beyond a two fold threshold between patient subgroups were identified by MALDI-TOF. Discrimininant analysis was used to build a model to predict patient subtype of the latter cohort.Results:Samespots software analysis of SF gel scans was used to highlight joint-specific proteins which were differentially expressed across disease classifications. Hierarchical clustering based on the expression levels of a previously selected set of 40 proteins matched across the three clinical subgroups segregates the polyarticular from the oligoarticular patients (Fig 1). The constructed statistical model classified each of the independent ‘test’ patient cohort into the respective disease subgroups. Proteolytic fragments of apolipoproteins, complement component C3c, haptoglobin and transferrin were identified (p
    LanguageEnglish
    Title of host publicationUnknown Host Publication
    Number of pages1
    Publication statusPublished - Nov 2008
    EventAmerican College of Rheumatology Annual Scientific Meeting - San Francisco, California
    Duration: 1 Nov 2008 → …

    Conference

    ConferenceAmerican College of Rheumatology Annual Scientific Meeting
    Period1/11/08 → …

    Fingerprint

    Juvenile Arthritis
    Proteome
    Synovial Fluid
    Joints
    Proteins
    Complement C3c
    Gels
    Haptoglobins
    Apolipoproteins
    Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Statistical Models
    Transferrin
    Secondary Prevention
    Autoimmune Diseases
    Cluster Analysis
    Electrophoresis
    Chronic Disease
    Coloring Agents
    Software

    Keywords

    • Juvenile arthritis
    • synovial fluid
    • proteome
    • bioinformatics

    Cite this

    Gibson, D. S., Rooney, M. E., Rosenkranz, M. E., Hirsch, R., Scaife, C., & Pennington, S. (2008). Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort. In Unknown Host Publication
    Gibson, D.S. ; Rooney, M.E. ; Rosenkranz, M.E. ; Hirsch, R. ; Scaife, C. ; Pennington, S. / Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort. Unknown Host Publication. 2008.
    @inproceedings{e21b27d8d3274d629454a7ac77c52ea4,
    title = "Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort",
    abstract = "Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. In a prior study, the synovial fluid (SF) proteome of an oligoarticular patient subgroup was compared to patients who show a spread of disease in the first year to involve new joints, the extended oligoarticular subgroup. Current laboratory tests are unable to flag those patients at a higher risk of disease spread to multiple joints, who could benefit form earlier therapy to prevent joint damage. This study investigated whether profiling of the SF proteome based a difference gel electrophoresis (DIGE) approach could differentiate between subgroups of this chronic disease.Methods:To construct a predictive model, SF samples from 22 JIA patients were analysed: 10 oligo-, 5 extended oligo- and 7 polyarticular disease. Samples from each patient were labeled with Cy dyes and subjected to protein separation by 2-DE. The predictive value of using a panel of SF proteins to stratify patients was tested on an independent pool of 28 JIA patients: 13 oligo-, 5 extended oligo- and 10 polyarticular disease. Protein spots of interest which over expressed beyond a two fold threshold between patient subgroups were identified by MALDI-TOF. Discrimininant analysis was used to build a model to predict patient subtype of the latter cohort.Results:Samespots software analysis of SF gel scans was used to highlight joint-specific proteins which were differentially expressed across disease classifications. Hierarchical clustering based on the expression levels of a previously selected set of 40 proteins matched across the three clinical subgroups segregates the polyarticular from the oligoarticular patients (Fig 1). The constructed statistical model classified each of the independent ‘test’ patient cohort into the respective disease subgroups. Proteolytic fragments of apolipoproteins, complement component C3c, haptoglobin and transferrin were identified (p",
    keywords = "Juvenile arthritis, synovial fluid, proteome, bioinformatics",
    author = "D.S. Gibson and M.E. Rooney and M.E. Rosenkranz and R. Hirsch and C. Scaife and S. Pennington",
    year = "2008",
    month = "11",
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    Gibson, DS, Rooney, ME, Rosenkranz, ME, Hirsch, R, Scaife, C & Pennington, S 2008, Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort. in Unknown Host Publication. American College of Rheumatology Annual Scientific Meeting, 1/11/08.

    Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort. / Gibson, D.S.; Rooney, M.E.; Rosenkranz, M.E.; Hirsch, R.; Scaife, C.; Pennington, S.

    Unknown Host Publication. 2008.

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    TY - GEN

    T1 - Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort

    AU - Gibson, D.S.

    AU - Rooney, M.E.

    AU - Rosenkranz, M.E.

    AU - Hirsch, R.

    AU - Scaife, C.

    AU - Pennington, S.

    PY - 2008/11

    Y1 - 2008/11

    N2 - Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. In a prior study, the synovial fluid (SF) proteome of an oligoarticular patient subgroup was compared to patients who show a spread of disease in the first year to involve new joints, the extended oligoarticular subgroup. Current laboratory tests are unable to flag those patients at a higher risk of disease spread to multiple joints, who could benefit form earlier therapy to prevent joint damage. This study investigated whether profiling of the SF proteome based a difference gel electrophoresis (DIGE) approach could differentiate between subgroups of this chronic disease.Methods:To construct a predictive model, SF samples from 22 JIA patients were analysed: 10 oligo-, 5 extended oligo- and 7 polyarticular disease. Samples from each patient were labeled with Cy dyes and subjected to protein separation by 2-DE. The predictive value of using a panel of SF proteins to stratify patients was tested on an independent pool of 28 JIA patients: 13 oligo-, 5 extended oligo- and 10 polyarticular disease. Protein spots of interest which over expressed beyond a two fold threshold between patient subgroups were identified by MALDI-TOF. Discrimininant analysis was used to build a model to predict patient subtype of the latter cohort.Results:Samespots software analysis of SF gel scans was used to highlight joint-specific proteins which were differentially expressed across disease classifications. Hierarchical clustering based on the expression levels of a previously selected set of 40 proteins matched across the three clinical subgroups segregates the polyarticular from the oligoarticular patients (Fig 1). The constructed statistical model classified each of the independent ‘test’ patient cohort into the respective disease subgroups. Proteolytic fragments of apolipoproteins, complement component C3c, haptoglobin and transferrin were identified (p

    AB - Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. In a prior study, the synovial fluid (SF) proteome of an oligoarticular patient subgroup was compared to patients who show a spread of disease in the first year to involve new joints, the extended oligoarticular subgroup. Current laboratory tests are unable to flag those patients at a higher risk of disease spread to multiple joints, who could benefit form earlier therapy to prevent joint damage. This study investigated whether profiling of the SF proteome based a difference gel electrophoresis (DIGE) approach could differentiate between subgroups of this chronic disease.Methods:To construct a predictive model, SF samples from 22 JIA patients were analysed: 10 oligo-, 5 extended oligo- and 7 polyarticular disease. Samples from each patient were labeled with Cy dyes and subjected to protein separation by 2-DE. The predictive value of using a panel of SF proteins to stratify patients was tested on an independent pool of 28 JIA patients: 13 oligo-, 5 extended oligo- and 10 polyarticular disease. Protein spots of interest which over expressed beyond a two fold threshold between patient subgroups were identified by MALDI-TOF. Discrimininant analysis was used to build a model to predict patient subtype of the latter cohort.Results:Samespots software analysis of SF gel scans was used to highlight joint-specific proteins which were differentially expressed across disease classifications. Hierarchical clustering based on the expression levels of a previously selected set of 40 proteins matched across the three clinical subgroups segregates the polyarticular from the oligoarticular patients (Fig 1). The constructed statistical model classified each of the independent ‘test’ patient cohort into the respective disease subgroups. Proteolytic fragments of apolipoproteins, complement component C3c, haptoglobin and transferrin were identified (p

    KW - Juvenile arthritis

    KW - synovial fluid

    KW - proteome

    KW - bioinformatics

    M3 - Conference contribution

    BT - Unknown Host Publication

    ER -

    Gibson DS, Rooney ME, Rosenkranz ME, Hirsch R, Scaife C, Pennington S. Validation of JIA Patient Stratification by Synovial Proteome Profiles in an Independent Cohort. In Unknown Host Publication. 2008