Rheumatology in the era of precision medicine: synovial tissue molecular patterns and treatment response in rheumatoid arthritis

Abstract

Purpose of review A critical unmet need in rheumatoid arthritis (RA) is the identification of biomarkers that predict which of the available medications will be most effective for an individual in order to lower disease activity sooner than is afforded by the current treat-to-target approach. Here we will discuss recent reports examining the potential for synovial tissue molecular, cellular, and spatial profiling in defining objective measures of treatment response and therein developing personalized medicine for RA. Recent findings Recent high-dimensional molecular profiling of RA synovium has provided unprecedented resolution of the cell types and pathways in tissues affected by rheumatic diseases. Heightened attention to tissue architecture is also emerging as a means to classify individual disease variation that may allow patients to be further stratified by therapeutic response. Although this wealth of data may have already pinpointed promising biomarkers, additional studies, likely including tissue-based functional drug response assays, will be required to demonstrate how the complex tissue environment responds. Summary Molecular, cellular, and more recently spatial profiling of the RA synovium are uncovering fundamental features of the disease. Current investigations are examining whether this information will provide meaningful biomarkers for individualized medicine in RA.

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

“…Furthermore, tissue-based in vitro models, coupled with scRNA-seq will enable better understanding of the complex mechanism of drug failure or response, as well as help identify novel therapeutic targets. For example, ex vivo tissue models, 3D models, or organoids could be used to identify novel drug candidates or serve as screening platforms ( 117 ). A 3D organoid co-culture of synovial fibroblasts and endothelial cells has yielded results ( 58 ) of the NOTCH3 signaling cascade, that could be an important novel therapeutic target in RA.…”