Abstract
RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.
Highlights
Concerns have been raised related to the sensitivity of some multiplex solid-phase assays [12] as well as interference from heterophilic antibodies [12,13,14,15,16,17,18,19]. This is of particular relevance in autoimmune disease where rheumatoid factor (RF), a heterophilic autoantibody directed against the Fc portion of IgG is present notably in Rheumatoid Arthritis (RA) [12, 20,21,22,23,24,25]
In individuals who donated serum samples and later developed RA, a multiplex study showed significant increased levels of cytokines related to T cell activation (IL-2, IL6), inflammation (IL-1beta, IL-1RA, and tumor necrosis factor (TNF)-alpha), Th1 (IL-12 and IFN-gamma), Th2 (IL-4, IL-13, and eotaxin), and immune regulation (IL-10), while chemokines, stromal cell-derived cytokines, and angiogenic-related markers were elevated in patients after the development of RA rather than in individuals before the onset of RA [219]
The assessment of the impact of using the biomarker on general health is an essential step to guarantee the uptake of the biomarker into clinical practice and to further optimise its use
Summary
Biomarkers allowing the selection of an optimal drug for a particular patient (acknowledging that certain subset of patients respond better to certain drug than others) may represent another essential step in patients screening that would notably allow personalised medicine models to be developed, tailoring therapy to the individual, shortening time from onset to effective treatment, improving cost and risk-benefit ratios of drugs, and achieving high response rate with minimal toxicity [10]; in patients with long-standing RA heterogeneity in disease presentation, there remains a major obstacle even when using biomaterial as close to the disease site as synovial tissue [11]. Later in the disease continuum, tolerability for more invasive procedure such as fluid aspiration or biopsy collection would provide material reflecting the disease site more closely allowing for individual variability to be taken into account for a personalised medicine approach
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