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Microscopic measurement of inflammation in synovial tissue: inter-observer agreement for manual quantitative, semiquantitative and computerised digital image analysis
  1. Terence Rooney1,
  2. Barry Bresnihan1,
  3. Ulf Andersson2,3,
  4. Martina Gogarty1,
  5. Maarten Kraan3,
  6. H Ralph Schumacher4,
  7. Ann-Kristin Ulfgren2,3,
  8. Douglas J Veale5,
  9. Peter P Youssef6,
  10. Paul P Tak3
  1. 1
    Department of Rheumatology, St. Vincent’s University Hospital, Dublin, Ireland
  2. 2
    Rheumatology Research Laboratory, Karolinska Hospital, Stockholm, Sweden
  3. 3
    Division of Clinical Immunology and Rheumatology, Academic Medical Centre, Amsterdam, The Netherlands
  4. 4
    Department of Rheumatology, VA Medical Centre, Philadelphia, USA
  5. 5
    Rheumatology Research Unit, University of Leeds, Leeds, UK
  6. 6
    Department of Pathology, University of New South Wales, Sydney, Australia
  1. Professor Barry Bresnihan, Department of Rheumatology, St. Vincent’s University Hospital, Dublin 4, Ireland; b.bresnihan{at}svcpc.ie

Abstract

Objectives: To evaluate inter-observer agreement for microscopic measurement of inflammation in synovial tissue using manual quantitative, semiquantitative and computerised digital image analysis.

Methods: Paired serial sections of synovial tissue, obtained at arthroscopic biopsy of the knee from patients with rheumatoid arthritis (RA), were stained immunohistochemically for T lymphocyte (CD3) and macrophage (CD68) markers. Manual quantitative and semiquantitative scores for sub-lining layer CD3+ and CD68+ cell infiltration were independently derived in 6 international centres. Three centres derived scores using computerised digital image analysis. Inter-observer agreement was evaluated using Spearman’s Rho and intraclass correlation coefficients (ICCs).

Results: Paired tissue sections from 12 patients were selected for evaluation. Satisfactory inter-observer agreement was demonstrated for all 3 methods of analysis. Using manual methods, ICCs for measurement of CD3+ and CD68+ cell infiltration were 0.73 and 0.73 for quantitative analysis and 0.83 and 0.78 for semiquantitative analysis, respectively. Corresponding ICCs of 0.79 and 0.58 were observed for the use of digital image analysis. All ICCs were significant at levels of p<0.0001. At each participating centre, use of computerised image analysis produced results that correlated strongly and significantly with those obtained using manual measurement.

Conclusion: Strong inter-observer agreement was demonstrated for microscopic measurement of synovial inflammation in RA using manual quantitative, semiquantitative and computerised digital methods of analysis. This further supports the development of these methods as outcome measures in RA.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    DMARD
    disease-modifying antirheumatic drug
    ICC
    intraclass correlation coefficient
    RA
    rheumatoid arthritis

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