Synovial biopsies in inflammatory arthritis: precision medicine in rheumatoid arthritis

ABSTRACT

Introduction: Synovial tissue (ST) is composed of a lining and sublining layer and is the target tissue involved in the inflammatory arthritides (IA), in which there is lining layer hyperplasia, inflammatory cell influx, macrophage recruitment and change in number and behavior of lining fibroblasts. Understanding synovial pathology has been critical in providing insights into pathogenetic mechanisms of disease and therapeutics. Pathobiological insights into ST have been underpinned by progress in molecular analytic methods; research in this area holds promise in individualizing treatment and optimizing response.

Areas covered: We explore ST in IA and cover in-depth the utility of synovial biopsy and ST heterogeneity. We review recent advances in ST research and discuss implications with regards to therapeutic response. Finally, we provide perspectives on the identification of new drug targets and new diagnostic and prognostic markers.

Expert opinion: ST holds the potential to individualize therapy by detecting biomarkers of diagnosis, therapeutic choice, and treatment modification in IA. Advances in molecular biology including high-throughput omics are likely to provide information that has hitherto remained unknown. ST analyzes pre- and post-treatment needs to be standard of care; only by routinely collecting and analyzing ST will we achieve the precision medicine outcomes described herein.

KEYWORDS:

• Rheumatoid arthritis
• synovial biopsy

Article Highlights

• Synovial tissue (ST) in the inflammatory arthritides (IA), and in particular in rheumatoid arthritis (RA) is characterized by considerable heterogeneity. This heterogeneity includes differences in lining layer hypertrophy, degree of neo-angiogenesis, and infiltration of immune cells; inflammatory infiltrate varies with regards to cell type, number, function and spatial orientation.

• Recent literature suggests different RA ‘pathotypes’ including diffuse, myeloid, lymphoid/follicular, and pauci-immune and follicular which may be associated with differential therapeutic response

• Major advances in the processing and analyzes of ST have enabled comprehensive interrogation of cellular subsets and inflammatory pathways in the pathogenesis of RA.

• Important cellular subsets associated with RA pathogenesis include T cells, B cells, synovial fibroblasts and synovial macrophages; recent advances in single-cell RNA sequencing (RNASeq) and mass cytometry have facilitated discovery of novel subsets such as T peripheral helper (T_PH) cells.

• Analyses of ST hold promise in the identification of biomarkers that will help choice of and predict response to an individual therapeutic agent. Recent developments in high-throughput technology such as imaging mass cytometry, single-cell RNASeq and antigen receptor sequencing provide new methodologies which will serve to assist in the search for such a test.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or a financial conflict with the subject matter or materials discussed in the manuscript.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

We acknowledge that A.S. is supported by funding from the 2019 Arthritis Australia: Bruce Miller/Australian Rheumatology Association Post-Doctoral Fellowship.