Related Experiment Video
Updated: Jul 17, 2026
A Pre-Clinical Model of Synovitis Using Ex vivo Human Synovial Tissue with Preserved Function and Architecture
Published on: March 20, 2026
Interobserver variability in synovial tissue biopsy markers in Rheumatoid Arthritis: Results from OMERACT special
Mario Ferraioli1, Annabelle Small2, Stefano Alivernini3
1School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Objectives:
to evaluate interobserver agreement in synovial tissue (ST) biopsy histology and immunohistochemistry (IHC) analysis across expert centers, and the influence of observers' experience on interobserver agreement.
Methods:
ST slides, collected from 38 biologic-naïve rheumatoid arthritis patients, stained for H&E, FVIII, CD68, CD3 and CD19/20, were uploaded to an online platform. Using semiquantitative analysis, independent observers scored ST slides for immune and vascularity markers (0 to 4), and Krenn's synovitis score (0 to 9). Presence of lymphoid aggregates and synovial pathotype were also recorded. After the initial scoring, a modified eDelphi process was conducted to reach consensus on a shared scoring approach among observers, followed by a second scoring. Interobserver agreement was assessed with Kappa coefficients.
Results:
Initial scoring showed variability across observers and centres, with higher agreement for immune markers (e.g. kappa for CD19/20=0.737; CD3=0.713) compared to vascular ones (FVIII=0.392, H&E = 0.316). Stratifying by observers' experience revealed lower agreement among highly experienced observers compared with low and intermediate-experienced observers on specific markers. After discussion, a modified eDelphi process was conducted, and consensus on adopting a maximum-score approach (the highest score observable on the slide as the final scoring) for semiquantitative parameters was reached. A rescoring exercise, applying this principle, demonstrated improved agreement among observers, across most parameters (CD68= 0.684, Krenn's score 0.545), although variability persists for certain parameters.
Conclusion:
This study demonstrates that consensus-based methods can improve interobserver agreement in ST histology and IHC scoring across centres. Adoption of a maximum-score approach among observers represents a further step toward standardization of ST biopsy analysis, and may support its broader application STATEMENT OF CLINICAL SIGNIFICANCE: Histological and immunohistochemical analysis of synovial tissue (ST) biopsy is a promising tool in rheumatoid arthritis (RA), both in translational and clinical research. Notably, the differences in ST biopsy evaluation and interpretation persist across different centres of excellence hampers its widespread clinical application and use in multicentre trials. Our study demonstrates that consensus-based approaches, particularly the adoption of a maximum-score principle, can improve interobserver agreement of ST scoring across centres. Our findings represent a critical step toward the standardization of ST biopsy analysis.
