Abstract
BackgroundThe B cell chemoattractant CXCL13 is a promising biomarker in rheumatoid arthritis (RA), with a plausible role in supporting diagnosis, monitoring disease activity and as a prognostic value. It is a key chemokine driving the formation of lymphoid follicles within the inflamed synovium. The objective of this systematic review was to evaluate the role of CXCL13 as a viable biomarker in RA.MethodsWe conducted a systematic literature review of all published cohort and randomised controlled trials evaluating the role of CXCL13 in RA. The primary outcomes were; i) CXCL13 levels in RA patients compared to healthy controls, ii) the correlation between CXCL13 and markers of disease activity, and iii) the association between CXCL13 and treatment response.ResultsThe search produced 278 articles, of which 31 met the inclusion criteria. Of the 12 studies evaluating CXCL13 expression in early or established RA, all reported higher levels than that seen in healthy controls. Twelve of sixteen studies reported a weakly positive correlation between CXCL13 and markers of disease activity including DAS28 and swollen joint count, with rho values between 0.20–0.67. In 2 studies, CXCL13 levels correlated with ultrasonographic evidence of synovitis. Eighteen studies assessed CXCL13 in response to therapeutic intervention. The majority signified a fall in levels in response to treatment including biologics and Janus kinase (JAK) inhibition. In some, this reduction was only seen in treatment responders. High CXCL13 levels predicted failure to achieve disease remission with csDMARDs. The evidence for treatment prediction with biologics was conflicting.ConclusionDespite evidence to suggest a role in diagnosing RA and in detecting synovitis, the heterogeneity of studies included in this review limit our ability to draw robust conclusions. At present there are inadequate results to justify the routine use of CXCL13 as a biomarker in RA routine clinical practice.
Highlights
The B cell chemoattractant CXCL13 is a promising biomarker in rheumatoid arthritis (RA), with a plausible role in supporting diagnosis, monitoring disease activity and as a prognostic value
The classical paradigm of RA pathogenesis is centred on the role of the CD4+ T cells, it is clear that B cells demonstrate a vital role including cytokine secretion, antigen presentation, and interaction with other
In this study we found that CXCL13 levels correlated with swollen joint counts and ultrasound findings of synovitis
Summary
The B cell chemoattractant CXCL13 is a promising biomarker in rheumatoid arthritis (RA), with a plausible role in supporting diagnosis, monitoring disease activity and as a prognostic value. It is a key chemokine driving the formation of lymphoid follicles within the inflamed synovium. It is not sensitive to short-term changes, with a slow response to the acute phase reaction leading to false negatives in an early inflammatory process [5] Both CRP and ESR lack sensitivity in patients with limited small joint or predominantly lower limb involvement and in those receiving immunosuppression with steroids or drugs that target interleukin-6 (IL-6) e.g. tocilizumab [6]. There is a current need for a biomarker with improved sensitivity which can aid diagnosis, monitor disease activity and provide prognostic value
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