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

Abstract

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.

Keywords: imaging; pathology; personalized medicine; rheumatoid arthritis; synovial membrane.

Figure 1

Ectopic lymphoneogenesis within the rheumatoid synovial membrane. The synovial inflammatory cell infiltrate has been demonstrated to organize into discrete organized clusters clearly visible following routine hematoxylin and eosin staining (A,B). The aggregate is primarily composed of T cells [CD3, (C,D)] and B cells [CD20, (E,F)] with a central follicular dendritic cell network [CD21, (G,H)]. Plasma cells [CD138, (I,J)] are shown surrounding the aggregate. Sequentially cut 3 µm sections of paraffin embedded rheumatoid arthritis (RA) synovial tissue from a patient with early RA are shown. Arrows indicate regions of positively stained cells. Left hand panel 4× magnification, right hand panel 20×, scale bar 200 µm.

Figure 2

Mechanisms of disruption of ectopic lymphoneogenesis within rheumatoid synovial tissue via currently licensed biologic agents for rheumatoid arthritis (RA). Disruption of ectopic lymphoneogenesis within the rheumatoid synovial membrane may be mediated by a number of biologic agents licensed for the treatment of RA and, therefore, has a putative role as a biomarker of response/resistance to biologic therapies. Rituximab induces death of CD20+ B cells via Ab or cell-mediated cytotoxicity, phagocytosis, or cell lysis. Abatacept, a CTLA-Ig fusion protein, prevents endogenous CTLA from binding to CD80/86 on B cells (functioning as antigen presenting cells) and so prevents co-stimulatory signals to the B cell. TNF inhibitors (TNFis) (inhibitors) such as infliximab bind to soluble and membrane-bound TNFα released by follicular dendritic cells (FDCs), and so inhibiting FDC-mediated B cell attraction. Tocilizumab inhibits binding of IL6 to its receptor, preventing IL6-mediated B cell proliferation and differentiation.