The Utility and Limitations of CRP, ESR and DAS28-CRP, in Appraising Synovial Inflammation in Rheumatoid Arthritis
Carl Orr 1, Aurelie Najm 1, Francis Young 1, Trudy McGarry 2, Monika Biniecka 1, Ursula Fearon 2 and Douglas J. Veale 1
1. Dublin Academic Medical Centre, Centre for Arthritis and Rheumatic Diseases, University College Dublin, Dublin, Ireland, 2. Molecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland
Identifying and quantifying inflammatory disease activity in RA remains a challenge. Many studies have suggested that a large proportion of patients may have active inflammation, but normal inflammatory markers.
Although various disease activity scores have been validated, most rely on biomarkers such as CRP and ESR.
Since the synovium is the principal target of inflammation in RA, we studied the synovium at the microscopic level, and relate CRP, ESR and DAS28-CRP with histological features of synovial biopsies, including specific cellular infiltrate. In this study, we examine the utility and limitations of these biomarkers, as well as the DAS28-CRP in appraising disease activity in RA.
223 consecutive rheumatoid arthritis reporting knee arthralgia underwent synovial sampling of the affected knee via needle arthroscopy. The synovium was examined by microscopy with H+E staining as well as immunohistochemistry, and related to the ESR, CRP and DAS28-CRP on samples taken
immediately before arthroscopy.
Although a statistically significant positive correlation was observed between
CRP and the level of inflammation in the biopsy retrieved (n = 197, rho = 0.43, CI 0.30–
0.54, p < 0.0001, figure 1), there was histological evidence of inflammation in the synovium in
49.4% of the patients who had a normal CRP (figure 2). A positive correlation was also observed
between ESR and the level of inflammation in the biopsy retrieved (n = 188, rho = 0.29,
CI 0.15–0.42 p < 0.0001). A statistically significant but weak positive correlation was
observed between the DAS28-CRP and synovial inflammation (n = 189, rho = 0.23, CI
0.09–0.37, p= 0.0011). Only the CD19 infiltrate in the synovium correlated with serum
CRP (n = 70, rho = 0.32, CI 0.08–0.52, p = 0.0068).
CRP has a moderately strong relationship with disease activity, but there
are significant pitfalls in the use of this biomarker in RA, and therefore a need interpret
CRP results judiciously. The results of this study underline the heterogeneity of RA, and
the need to develop improved panels of biomarkers, to better stratify RA, and to identify
the cohort for whom inflammatory activity cannot be measured accurately with CRP.