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. 2021 Mar 22;11(1):6583.
doi: 10.1038/s41598-021-86064-x.

Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis

Anne-Christine Bay-Jensen  1 , Asger Bihlet  2 , Inger Byrjalsen  3 , Jeppe Ragnar Andersen  2 , Bente Juhl Riis  2 , Claus Christiansen  3 , Martin Michaelis  4 , Hans Guehring  5 , Christoph Ladel  6 , Morten A Karsdal  7
Affiliations

Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis

Anne-Christine Bay-Jensen et al. Sci Rep. .

Abstract

The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3-8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5-16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0-4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.

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Conflict of interest statement

At the time of the analysis and manuscript write up ACBJ, AB, JRA and MAK were full-time employees and shareholders of Nordic Bioscience A/S, as privately-owned biotechnology company. IB was a full-time employee of Nordic Bioscience A/S. HG, MM and CL are shareholders and full-time employees at Merck KGaA. CC and BJR are the majority owners of Nordic Bioscience.

Figures

Figure 1
Figure 1
Baseline serum CRP and CRPM levels in early arthritis (E-RA), moderate to severe RA (MS-RA) and osteoarthritis (OA) patients compared to early RA patients. (A) Serum CRP levels and (B) serum CRPM levels. Grey vertical bars indicate the normal references ranges established in the central lab measuring the markers. Data are shown as IQR and differences are tested by ANCOVA using log transformed biomarker data adjusting for covariates (age, gender, race, VAS pain). Bonferroni corrected significance levels: **p < 0.01 and ****p < 0.0001.
Figure 2
Figure 2
ROC analyses of for separating OA from either E-RA or MS-RA including covariates (Age, gender, race, BMI* and VAS pain) or markers alone or in combination. *BMI was only available for the MS-RA and OA cohorts.
Figure 3
Figure 3
Overview for the osteoarthritis case–control study.
See this image and copyright information in PMC

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