Synovial Tissue: Turning the Page to Precision Medicine in Arthritis?

In the majority of joint diseases, changes in the organization of the synovial architecture appear early. Synovial tissue analysis might provide useful information for the diagnosis, especially in atypical and rare joint disorders, and might have a value in case of undifferentiated inflammatory arthritis, by improving disease classification. After patient selection, it is crucial to address the dialogue between the clinician and the pathologist for adequately handling the sample, allowing identifying histological patterns depending on the clinical suspicion. Moreover, synovial tissue analysis gives insight into disease progression helping patient stratification, by working as an actionable and mechanistic biomarker. Finally, it contributes to an understanding of joint disease pathogenesis holding promise for identifying new synovial biomarkers and developing new therapeutic strategies. All of the indications mentioned above are not so far from being investigated in everyday clinical practice in tertiary referral hospitals, thanks to the great feasibility and safety of old and more recent techniques such as ultrasound-guided needle biopsy and needle arthroscopy. Thus, even in rheumatology clinical practice, pathobiology might be a key component in the management and treatment decision-making process. This review aims to examine some essential and crucial points regarding why, when, where, and how to perform a synovial biopsy in clinical practice and research settings and what information you might expect after a proper patient selection.

Interleukin (IL)-17A has a direct contribution in early induction and late chronic stages of various inflammatory diseases. In vitro and in vivo experiments have first characterized its local effects on different cell types and then its systemic effects. For instance, IL-17 axis is now identified as a key driver of psoriasis through its effects on keratinocytes. Similar observations apply for rheumatoid arthritis (RA) where IL-17A triggers changes in the synovium that lead to synovitis and maintain local inflammation. These results have prompted the development of biologics to target this cytokine. However, while convincing studies are reported on the efficacy of IL-17 inhibitors in psoriasis, there are conflicting results in RA. Patient heterogeneity but also the involvement of mediators that regulate IL-17 function may explain these results. Therefore, new tools and concepts are required to identify patients that could benefit from these IL-17 targeted therapies in RA and the development of predictive biomarkers of response has started with the emergence of various bioassays. Current strategies are also focusing on synovial biopsies that may be used to stratify patients. From local to systemic levels, new approaches are developing and move the field of RA management into the era of precision medicine.