Heterogeneity of synovial tissue in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex autoimmune disease that is genetically and biologically heterogeneous. It is characterized by inflammatory arthritis with strong systemic electivity.

The treatment of patients with rheumatoid arthritis has evolved considerably in recent years thanks to the development and widespread use of biological disease-modifying anti-rheumatic drug therapies (bDMARDs) and, subsequently, with the more recent introduction of targeted synthetic DMARDs (tsDMARD) in the form of small inhibitory molecules.

However, although these drugs are of great help in rheumatic patients, up to 40% of patients fail to respond adequately and, a considerable percentage fail to achieve the therapy goal: clinical remission where appropriate or low disease activity ( 2.6 <DAS <3.2) (1).

In this case, personalized medicine, that is, adapting therapy to the individual patient (or simply “choosing the right drug for the right patient”), has the potential to improve response rates.

The synovium is the main target of inflammation in RA, undergoing marked pathological changes compared to healthy tissue. The study of RA synovial tissue offered cellular insights into multiple aspects of the disease, from identifying pathogenic processes and pathways to changes in tissue following effective treatment, allowing a better understanding of the drug’s mechanism of action ( 5).

Synovial tissue samples can be obtained via arthroscopy-guided biopsies or ultrasound.

In particular, the heterogeneity of subjects affected by RA can be found at the synovial level. RA synovitis is highly heterogeneous with different cellular and molecular signatures.

Distinct patterns have been recognized in recent years, mainly based on the composition, organization and location of cell infiltrates.

Recent studies have revealed synovial pathotypes (biological variants) of RA (24), namely lymphoid, myeloid and fibroid variants.

The lymphoid pathotype is characterized by lymphoid infiltrates, which can be diffuse (small groups of loosely arranged B and T lymphocytes) or follicular (large aggregates of B and T lymphocytes organized in clusters) (25).

The cellular composition of the tissue defined as myeloid pathotype shows less abundant B and T cell aggregates than the lymphoid subgroup and the presence of sublining macrophages.

Finally, the fibrous pathotype does not present lymphocyte aggregates but only a poor immune infiltration.

In recent years, the emphasis on synovial tissue is becoming more and more marked and the reason is quite clear; the synovium is the primary information site of the RA from which it is possible to delineate the subtypes of tissue and therefore of disease.

The richness of data combined with sophisticated executive and analytical techniques allows us at iCareX, a leader in the field of medicine personalized, to accompany autoimmune diseases towards more advanced and effective treatments and cures.

Today with particular attention to Rheumatoid Arthritis.




  1. Nam J, Winthrop K, van Vollenhoven RF, Pavelka K, Valesini G, Hensor E, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic review of the literature informing EULAR recommendations for the management of RA. Ann Rheum Dis. (2010) 69: 976–86. doi: 10.1136 / ard.2009.126573


  1. Tak P. Lessons learned from synovial tissue response to antirheumatic treatment. Rheumatology. (2000) 39: 817-20. doi: 10.1093 / rheumatology / 39.8.817


  1. Dennis G, Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF, Hackney JA, et al. Synovial phenotypes in rheumatoid arthritis are correlated with the response to biological therapies. Therapy for the resolution of arthritis. (2014) 16: R90. doi: 10.1186 / ar4555


  1. Orr C, Najm A, Biniecka M, McGarry T, Ng Ct, Young F, et al. Synovial immunophenotype and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis: relationship with treatment response and radiological prognosis. Rheumatol arthritis. (2017) 69: 2114–23. doi: 10.1002 / item 40218

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