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. 2018 Aug 3:5:185.
doi: 10.3389/fmed.2018.00185. eCollection 2018.

The Utility and Limitations of CRP, ESR and DAS28-CRP in Appraising Disease Activity in Rheumatoid Arthritis

Carl K Orr  1 , Aurelie Najm  1 , Francis Young  1 , Trudy McGarry  2 , Monika Biniecka  1 , Ursula Fearon  2 , Douglas J Veale  1
Affiliations

The Utility and Limitations of CRP, ESR and DAS28-CRP in Appraising Disease Activity in Rheumatoid Arthritis

Carl K Orr et al. Front Med (Lausanne). .

Abstract

Introduction: Identifying and quantifying inflammatory disease activity in rheumatoid arthritis 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 to a large degree on biomarkers such as CRP and ESR. In this study, we examine the utility and limitations of these biomarkers, as well as the DAS28-CRP in appraising disease activity in RA. Methods: Two hundred and twenty three 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 blood samples taken immediately before arthroscopy. Results: 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), there was histological evidence of inflammation in the synovium in 49.4% of the patients who had a normal CRP. 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). Conclusion: 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.

Keywords: disease activity; inflammatory biomarkers; rheumatoid arthritis; synovial biopsy; synovium.

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Figures

Figure 1
Figure 1
Representative photomicrographs of synovial tissue stained with haematoxylin and eosin and immunohistochemistry, for (A) CD3, scoring 3, original magnification 1 OX, and (B) CD4, scoring 1, original magnification 20X.
Figure 2
Figure 2
Correlation of CRP with tissue inflammation scores (A) correlation of CRP levels with tissue inflammation score on H+E staining. n = 197, rho = 0.43, Cl 0.30–0.54, ****p < 0.0001. (B) comparison of the CRP levels across the 3-point tissue inflammation score using Kruskaii-Wallis test, p = 0.0002.
Figure 3
Figure 3
Correlation of ESR with tissue inflammation scores (A) correlation of ESR with tissue inflammation score on H+E staining. n = 188, rho = 0.29, Cl 0.15–0.42 p < 0.0001. (B) comparison of the ESR across the 3-point tissue inflammation score using Kruskaii-Wallis test, p = 0.0001.
Figure 4
Figure 4
Correlation of DAS28-CRP with tissue inflammation scores (A) correlation of DAS28-CRP with tissue inflammation score on H+E staining (n = 189, rho = 0.23, Cl 0.09–0.37, p = 0.0011). (B) comparison of the DAS28-CRP levels across the 3-point tissue inflammation score using One-Way ANOVA test, p = 0.0009.
Figure 5
Figure 5
(A) In those with a normal CRP (<5 mg/L) at time of biopsy (n = 75), 49.4% had histological evidence of inflammation in the synovial tissue retrieved. (B) In those with a DAS28-CRP (< 2.6) at time of biopsy (n = 14), 71.4% had histological evidence of inflammation in the synovial tissue retrieved. (C) A comparison of the performance of CRP, ESR, and DAS28-CRP in identifying histological inflammation.
Figure 6
Figure 6
Correlation between CRP and CD19+ cellular infiltrate in the synovial sublining (n = 70, rho = 0.32, Cl 0.08–0.52, p = 0.0068).
See this image and copyright information in PMC

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