Review Article | Published:

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

Nature Reviews Rheumatology volume 13, pages 463475 (2017) | Download Citation

  • An Erratum to this article was published on 22 September 2017
  • A Corrigendum to this article was published on 19 December 2017

This article has been updated


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.

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.

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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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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


  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, 1649–035, Lisbon, Portugal.

    • Elsa Vieira-Sousa
    •  & João E. Fonseca
  3. University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, 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. Arthritis Unit, Rheumatology Department, Hospital Clínic, IDIBAPS, Villarroel, 170, 08036 Barcelona, Spain.

    • Juan D. Cañete
  7. Rheumatology Unit, Department of Medicine (Solna), Karolinska Institute and Karolinska University Hospital, 171 76 Stockholm, 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, 1100 DE, Amsterdam, 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, 5700 Svendborg, Denmark.

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

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

    • Benoit Le Goff
    •  & Aurélie Najm
  17. Rheumatology and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology, IRCCS Policlinico San Matteo Foundation/University of Pavia, P.le Golgi 19, 27100 Pavia, 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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Douglas J. Veale.


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.


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


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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