Abstract
Purpose of reviewRheumatoid arthritis is a systemic disease of evolving immune dysregulation that culminates in joint destruction and disability. The principle by which pro-inflammatory cytokines may be therapeutically targeted to abrogate disease is well established, but has yet to translate into reliable cures for patients. Emerging insights into cytokine-mediated pathobiology during rheumatoid arthritis development are reviewed, and their implications for future treatment strategies considered.Recent findingsAccumulating data highlight cytokine perturbations before the clinical onset of rheumatoid arthritis. Some of these have now been linked to the arthritogenic activation of autoantibodies and associated pain and bone destruction in affected joints. These observations suggest cytokines may trigger the transition from systemic immunity to arthritis. Cytokine exposure could furthermore ‘prime’ synovial stromal cells to perpetuate a dominant pro-inflammatory environment. By facilitating cross-talk between infiltrating immune cells and even sustaining ectopic lymphoid structure development in some cases, cytokine interplay ultimately underpins the failure of arthritis to resolve.SummarySuccessful therapeutic stratification will depend upon an increasingly sophisticated appreciation of how dominant players amongst cytokine networks vary across time and anatomical space during incipient rheumatoid arthritis. The prize of sustained remission for all patients justifies the considerable effort required to achieve this understanding.
Highlights
Rheumatoid arthritis is a systemic inflammatory disease that primarily affects the synovial joints, and for which there is no known cure
The concept that distinct subtypes of the syndrome are delineated by the presence or absence of circulating antibodies to citrullinated peptides (ACPAs) has gained traction recently [1,2]
The broad inflammatory features of rheumatoid synovitis are well described [27&], but an emergent literature has set ‘early synovitis’ apart as a distinct, transitional pathological phase in rheumatoid arthritis development, during which cytokine cross-talk between cells of the stroma, endothelium and the immune system may uniquely effect the failure of inflammation to resolve within the joint
Summary
Rheumatoid arthritis is a systemic inflammatory disease that primarily affects the synovial joints, and for which there is no known cure. Mechanisms behind the development of seronegative rheumatoid arthritis remain far less well understood, its heritability and association with smoking both apparently modest by comparison, but a recent familial aggregation study suggests the National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon, Tyne, UK.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
