Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease targeting the joints. Current treatment strategies are based on clinical, biological and radiological features, yet still fail to reach the goal of early low disease activity in a significant number of cases. Hence, there is a need for refining current treatment algorithms, using accurate markers of response to therapy. Because RA induces histological and molecular alterations in the synovium even before apparition of clinical symptoms, synovial biopsies are a promising tool in the search of such new biomarkers. Histological and molecular characteristics of RA synovitis are heterogeneous. Variations in synovial lining layer hyperplasia, in cellular infiltration of the sublining by immune cells of myeloid and lymphoid lineages, and in molecular triggers of these features are currently categorized using well-defined pathotypes: myeloid, lymphoid, fibroid and pauci-immune. Here, we first bring the plasticity of RA synovitis under scrutiny, i.e., how variations in synovial characteristics are associated with relevant clinical features (disease duration, disease activity, effects of therapies, disease severity). Primary response to a specific drug could be, at least theoretically, related to the representation of the molecular pathway targeted by the drug in the synovium. Alternatively, absence of primary response to a specific agent could be due to disease severity, i.e., overrepresentation of all synovial molecular pathways driving disease activity overwhelming the capacity of any drug to block them. Using this theoretical frame, we will highlight how the findings of previous studies trying to link response to therapy with synovial changes provide promising perspectives on bridging the gap to personalized medicine in RA.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly joints
Using a set of 100 transcripts, based on their ability to discriminate RA from other inflammatory disorders in synovial tissue, we found that an accurate diagnosis of RA could be predicted in undifferentiated arthritis (UA) patients only when a combination of synovial transcriptomic and clinical data were combined, in line with the hypothesis that synovial samples rather display an undifferentiated synovial gene expression pattern when they originate from UA patients [41]
We looked at the link between synovial transcriptomic profiles and disease activity (DAS28CRP, CDAI, SDAI) in a series of 65 RA synovial biopsies [44] and found a strong correlation between all 3 measures and transcripts associated with an overwhelming lymphoid, and, to a lesser extent, myeloid (TNFα-dependent) signature
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly joints. RA diagnosis using the ACR/EULAR 2010 criteria relies on clinical and biological criteria [1, 2], resulting in early diagnosis and differentiation from other conditions. These results were not confirmed in later studies, performed on larger numbers of patients, in which no association was found between synovial lymphoid aggregates and clinical outcomes such as the development of erosions or increased disease activity [19, 22].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
