Targeting early changes in the synovial microenvironment:a new class of immunomodulatory therapy?

Objectives: Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA). Methods: Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed. Results: Tenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. Conclusions: Early changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression

Bio‐marker detection redundancy improves sensitivity

Abstract Liquid biopsy for biomarker detection has the potential to revolutionise the management of cancer by reducing the time that tumours grow and metastasize undetected and untreated. As a relatively less invasive test, the frequency of testing is constrained more by the cost and ease of analysis, which are connected to the specificity and sensitivity of the method of detection. A recent study by Zhao et al. in Clinical and Translational Medicine indicates that multiple forms of detection from the liquid biopsy sample may improve sensitivity and demonstrates that seemingly incremental advances in clinical practice can significantly impact patient outcomes