Biomarker profiling in rheumatoid arthritis: an investigation of markers of immune dysfunction and their relationship to disease phenotype

Abstract

Rheumatoid arthritis is an autoimmune disease in which various mediators of immune function play a vital role in the pathological process, influencing its development, progression and severity.

The aim of this study was to investigate the relationship between markers of immune dysfunction and the disease process. One of the main objectives was to identify key biomarkers involved in early RA (<1 year) and their association with disease measures and development of established disease (>5 years). Another objective was to determine the relationship between biomarkers of the peripheral circulation and the synovial joint, and to investigate the association of markers from both environments with disease activity and severity. The influence of smoking on biomarker expression and its relationship with disease activity and severity was also investigated.

Using ELISAs and bead-based multiplex assays, 41 mediators were analysed in the sera of early RA (n=86), established RA (n=77), OA (n=20), PsA (n=34) and ReA (n=26) patients as well as in paired sera and synovial fluid of 52 RA patients. Data were analysed using a variety of statistical methods including hierarchical clustering, principal component analysis, regression analysis and ROC analysis.

This study demonstrated the involvement of numerous interleukins, matrix remodelling mediators and pro inflammatory mediators in the disease process in both early and established RA, and enabled its differentiation from other arthritides. In addition, biomarkers from both the synovial fluid and the peripheral circulation were found to be associated with disease activity and severity. Cigarette smoking influenced biomarker expression in both the systemic and local environment, and a smoking associated biomarker profile was associated with worse disease.

This study reveals that RA is an extremely heterogeneous disease involving many mediators in a complex network which may include various pathological routes. Many of these biomarkers could potentially become new targets for disease intervention.