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  • Review Article
  • Published:

Synovial tissue research: a state-of-the-art review

Nature Reviews Rheumatology volume 13, pages 463–475 (2017)Cite this article

Subjects

A Corrigendum to this article was published on 19 December 2017

An Erratum to this article was published on 22 September 2017

This article has been updated

Key Points

  • Synovial tissue is the target tissue for autoimmune arthritides such as rheumatoid arthritis.

  • Synovial biopsy is a safe and well-tolerated procedure that is becoming more widely available.

  • There is a significant body of work from the past 30 years analysing the cellular and molecular changes in synovial tissue from patients with rheumatoid arthritis to identify specific biomarkers.

  • Technological advances in molecular and cellular analysis now provide new opportunities for defining new biomarkers and targets.

Abstract

The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.

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Figure 1: The macroscopic and microscopic appearance of rheumatoid synovial tissue.
Figure 2: Synovial tissue retrieval methods.
Figure 3: Synovial tissue immunostaining.
Figure 4: Ex vivo synovial tissue culture viability.

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Change history

  • 19 December 2017

    In the version of this article originally published, the author Sander W. Tas was erroneously omitted from the author list. This error has now been corrected in the online version of the article.

  • 22 September 2017

    In the original version of this article the name of one of the authors, Elsa Vieira-Sousa, was incorrectly given as Elsa Sousa. This error has now been corrected in the PDF and HTML versions of the article.

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Acknowledgements

We wish to thank all our colleagues in the European Synovitis Study Group and in the OMERACT group who have supported the development of synovial tissue research.

Author information

Authors and Affiliations

  1. Centre for Arthritis and Rheumatic Disease, University College Dublin, Dublin Academic Medical Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland

    Carl Orr & Douglas J. Veale

  2. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649–035, Portugal

    Elsa Vieira-Sousa & João E. Fonseca

  3. University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, 92093, California, USA

    David L. Boyle

  4. Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK

    Maya H. Buch & Paul Emery

  5. Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, West Midlands, B15 2TT, UK

    Christopher D. Buckley & Andrew Filer

  6. Rheumatology Department, Arthritis Unit, Hospital Clínic, IDIBAPS, Villarroel, 170, Barcelona, 08036, Spain

    Juan D. Cañete

  7. Department of Medicine (Solna), Rheumatology Unit, Karolinska Institute and Karolinska University Hospital, Stockholm, 171 76, Sweden

    Anca I. Catrina

  8. Cardiff University School of Medicine, Institute of Infection and Immunity, 1 st Floor, Tenovus Building, Heath Park, Cardiff, CF14 4XN, UK

    Ernest H. S. Choy

  9. Department of Molecular Rheumatology, Trinity College Dublin, University of Dublin, College Green, Dublin 2, Ireland

    Ursula Fearon & Trudy McGarry

  10. Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and Immunology Centre, Academic Medical Centre, University of Amsterdam, Room F4-105, POBox 22700, Amsterdam, 1100 DE, Netherlands

    Danielle Gerlag, Paul P. Tak & Sander W. Tas

  11. Clinical Unit Cambridge, GlaxoSmithKline, Cambridge, UK

    Danielle Gerlag

  12. Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Frances Humby & Constantino Pitzalis

  13. Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

    John D. Isaacs & Arthur Pratt

  14. Department of Medicine, Svendborg Hospital, Odense University Hospital, Valdemarsgade 53, Svendborg, 5700, Denmark

    Søren A. Just

  15. Université catholique de Louvain and Department of Rheumatology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, Bruxelles, 1200, Belgium

    Bernard R. Lauwerys

  16. Rheumatology Unit, Nantes University Hospital, Hôtel-Dieu, 1, place Alexis-Ricordeau, Nantes cedex 1, 44093, France

    Benoit Le Goff & Aurélie Najm

  17. Division of Rheumatology, Rheumatology and Translational Immunology Research Laboratories (LaRIT), IRCCS Policlinico San Matteo Foundation/University of Pavia, P.le Golgi 19, Pavia, 27100, Italy

    Antonio Manzo

  18. Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow, G12 8TA, UK

    Iain B. McInnes

  19. Rheumatology, Flinders University, GPO Box 2100, Adelaide, 5001, South Australia, Australia

    Malcolm Smith

  20. GlaxoSmithKline, Cambridge, UK

    Paul P. Tak

  21. Institute for Molecular Life Sciences, RadboudUMC, Theodoor Craanenlaan 11, Nijmegen, 6525 GA, Netherlands

    Rogier Thurlings

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Contributions

D.J.V., C.O., U.F., A.N., A.P., S.W.T. and J.E.F. researched data for the article, made a substantial contribution to the discussion of article content, wrote the manuscript, and reviewed and edited the manuscript before submission. E.V.-S., F.H., S.A.J., T. McG. and R.T. researched data for the article, wrote the manuscript, and reviewed and edited the manuscript before submission. A.F. researched data for the article, and reviewed and edited the manuscript before submission. B.R.L. wrote the manuscript, and reviewed and edited the manuscript before submission. D.L.B., M.H.B., C.D.B., J.D.C., A.I.C., E.H.C., P.E., D.G., J.D.I., B.L., A.M., I.B.M., C.P., M.S. and P.P.T. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Douglas J. Veale.

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Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Fibroblast-like synoviocytes

(FLSs). Also known as type B synovial lining cells, FLSs account for the majority of cells in the synovial lining layer.

Intimal lining layer

The lining of the synovium comprising a few cells without a basement membrane and which covers the nonarticular surface of the joint capsule.

Synovial sublining

A loose connective tissue that lies beneath the intimal lining of the synovium.

Pannus

A 'tumour-like' mass of hyperplastic synovial tissue that expands into the joint, invading into bone and cartilage.

Arthroplasty

Surgical reconstruction or replacement of a synovial joint.

Arthroscopic biopsy

Minimally invasive procedure to examine a synovial joint using an endoscope.

Ex-TH17 cells

T helper 17 (TH17) cells can switch to become ex-TH17 cells that no longer produce IL-17 but have the ability to produce IFNγ.

Positional memory

Cells might demonstrate different DNA 'fingerprints' depending on the site of the body at which they reside.

Undifferentiated arthritis

Inflammatory oligoarthritis or polyarthritis that does not conform to any of the recognized inflammatory arthritis types.

Disease stratification

The concept that a disease can be classified into distinct subsets that exhibit differential outcomes and responses, and that can each be labelled by a biomarker or a combination of biomarkers.

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Orr, C., Vieira-Sousa, E., Boyle, D. et al. Synovial tissue research: a state-of-the-art review. Nat Rev Rheumatol 13, 463–475 (2017). https://doi.org/10.1038/nrrheum.2017.115

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