Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction Models to Achieve Personalized Health Care in Rheumatoid Arthritis?

Although great progress has been made in the past decade toward understanding the pathogenesis of rheumatoid arthritis (RA), clinicians remain some distance from a goal of personalized health care. The capacity to diagnose RA early, predict prognosis, and moreover predict response to biologic therapies has been a research focus for many years. How currently available clinical prediction models can facilitate such goals is reviewed in this article. In addition, the role of current imaging techniques in this regard is also discussed. Finally, the authors review the current literature regarding synovial biomarkers and consider whether integration of synovial pathobiology into clinical prediction algorithms may enhance their predictive value

Generation of Recombinant Monoclonal Antibodies from Single B Cells Isolated from Synovial Tissue of Rheumatoid Arthritis Patients.

Ectopic lymphoid structure (ELS) can form in the target tissues of patients with chronic inflammatory autoimmune diseases such as rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Although it is still not clear why ELS form only in a subset of patients, it is well known that these structures can acquire features of ectopic germinal centers and contribute actively to the production of autoantibodies. Here, we describe a method to generate recombinant monoclonal antibodies from single ELS+ synovial tissue B cells obtained from RA patients. This chapter gives a detailed description of the method beginning from the mononuclear cell preparation from RA synovial tissue, single-cell sort of B cells by flow cytometry, amplification of the immunoglobulin (Ig) genes (both heavy- and light-chain genes) by PCR, and subsequent Ig gene expression vector cloning for full recombinant IgG1 monoclonal antibody (rmAb) production in vitro. The recombinant mAbs generated can be then characterized for (1) analysis of the Ig gene repertoires for clonal studies, (2) immunoreactivity profile, and (3) functional studies both in vitro and in vivo

Placental programming of anxiety in adulthood revealed by Igf2-null models

Imprinted, maternally silenced insulin-like growth factor-2 is expressed in both the foetus and placenta and has been shown to have roles in foetal and placental development in animal models. Here we compared mice engineered to be null for the placenta-specific P0 transcript (insulin-like growth factor-2-P0 KO) to mice with disruptions of all four insulin-like growth factor-2 transcripts, and therefore null for insulin-like growth factor-2 in both placenta and foetus (insulin-like growth factor-2-total KO). Both models lead to intrauterine growth restriction but dissociate between a situation where there is an imbalance between foetal demand and placental supply of nutrients (the insulin-like growth factor-2-P0 KO) and one where demand and supply is more balanced (the insulin-like growth factor-2-total KO). Increased reactivity to anxiety-provoking stimuli is manifested later in life only in those animals where there is a mismatch between placental supply and foetal demand for nutrients during gestation. Our findings further distinguish placental dysfunction from intrauterine growth restriction and reveal a role for the placenta in long-term programming of emotional behaviour