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THE IMPORTANCE OF THE STUDY OF THE SYNOVIA IN PATIENTS WITH RHEUMATOID ARTHRITIS

Synovial tissue is a key structure in the joint and represents a primary target of multiple pathologies characterized by different pathogenic mechanisms including: infectious, neoplastic and chronic immuno-inflammatory pathologies.

The synovium is the main target of inflammation in rheumatoid arthritis (RA).

Normal synovial tissue contains specialized fibroblast-like synoviocytes (FLS) interspersed with macrophages (2). In RA the synovial tissue becomes hypervascular and hyperplastic, this condition is mainly caused by the accumulation of FLS and macrophage cells in the synovial lining (3).

The development of new blood vessels (angiogenesis) allows the infiltration of immune cells such as T lymphocytes, B lymphocytes and monocytes;

angiogenesis transforms the synovial tissue into an aggressive “cloth” that characterizes the release of pro-inflammatory cytokines by macrophages, T and B cells which in turn stimulate the activation of synovial fibroblasts (FLS) and subsequent bone destruction.

In this regard, the inclusion of transcriptomic techniques in synovial tissue analysis presents interesting possibilities for a better understanding of the disease.

Most clinical research today focuses on prognosis and predicting treatment response in patients with rheumatoid arthritis. To better understand the obstacles to the clinical implementation of potential biomarkers, it is useful to critically evaluate the use of diagnostic tests that are currently delivered in current clinical practice (at this time, synovial tissue analysis is rarely used for differential diagnosis in patients with arthritis.)

There are several causes of arthritis and it is often problematic for the rheumatologist to discriminate between these.

In a first analysis, the doctor analyzes the development over time, the number and the pattern of the joints involved.

Second, investigations such as imaging studies and blood tests are done which can provide further clues for diagnosis.

Despite this, the rheumatologist is often unable to determine the diagnosis with certainty.

In this case, the analysis of the synovial tissue by means of RNA sequencing can be of help in the evaluation of arthritis, whose origin is undetermined, allowing the personal identification (on the patient) of specific traits such as specific markers (cellular and / or molecular).

The presence of expanded monocytes, T and B lymphocytes in the blood and synovial tissue of RA patients provides the basis for the development of new biological therapies including anti-cytokine antibodies and rituximab.

The existence of peculiar biological traits was confirmed by gene expression analyzes. In this context, overexpressed inflammatory genes could predict which drug therapies a patient is most likely to respond positively.

Recently, an RNA-based study of synovial tissue suggested that transcripts associated with lymphocyte aggregates are able to predict response to infliximab therapy (22).

The role of macrophages and T lymphocytes as response biomarkers is supported by gene expression analysis performed before and after rituximab treatment, showing that the clinical response was greater in patients with high expression of macrophage-associated synovial genes and T cells ( 23).

Recent technological advances are enabling a deeper molecular analysis of synovial tissue. New technologies have become faster, are of better value, and provide more detailed analysis of genes and proteins.

Therefore, over the past year, we at iCareX have developed cutting-edge techniques to analyze synovial biopsies in subsets of viable single cells allowing specific analysis of genes, proteins and functions of cells comprising the population in the tissue. synovial joint actively inflamed.

As we introduced in the article, RA is characterized by inflammation of the synovial tissue, which therefore represents the target tissue of autoimmune arthritis.

The study of the synovium could allow for a greater understanding of the pathogenesis of RA, enabling the development of a “precision medicine” approach with better therapy, ensuring patient differentiation, development of new therapeutic targets and development of specific biomarkers of response. 

References:

2. Smith MD, Barg E, Weedon H, Papengelis V, Smeets T, Tak PP, et al. . Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints. Ann Rheum Dis. (2003) 62: 303–7. 10.1136 / ard. 62.4.303

3. Tak PP, Smeets TJ, Daha MR, Kluin PM, Meijers KA, Brand R, et al. . Analysis of synovial cell infiltration in early rheumatoid synovial tissue in relation to local disease activity. Rheumate arthritis. (1997) 40: 217–25. 10.1002 / item 1780400206

22. Lindberg J, Wijbrandts CA, van Baarsen LG, Nader G, Klareskog L, Catrina A, et al. . The gene expression profile in the synovium as a predictor of the clinical response to infliximab treatment in rheumatoid arthritis. PLoS ONE. (2010) 5: e11310. 10.1371 / journal.pone.0011310

23. Gutierrez-Roelens I, Galant C, Theate I, Lories RJ, Durez P, Nzeusseu-Toukap A, et al. . Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium. Arthritis Rheum. (2011) 63: 1246–54. 10.1002 / article 30292

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