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. 2016 Jan 20:6:18421.
doi: 10.1038/srep18421.

Increased Dickkopf-1 in Recent-onset Rheumatoid Arthritis is a New Biomarker of Structural Severity. Data from the ESPOIR Cohort

Raphaèle Seror  1   2 , Saida Boudaoud  2 , Stephan Pavy  1 , Gaetane Nocturne  1   2 , Thierry Schaeverbeke  3 , Alain Saraux  4 , Philippe Chanson  5   6 , Jacques-Eric Gottenberg  7 , Valérie Devauchelle-Pensec  4 , Gabriel J Tobón  4 , Xavier Mariette  1   2 , Corinne Miceli-Richard  1   2
Affiliations

Increased Dickkopf-1 in Recent-onset Rheumatoid Arthritis is a New Biomarker of Structural Severity. Data from the ESPOIR Cohort

Raphaèle Seror et al. Sci Rep. .

Abstract

Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the world. RA is potentially disabling because chronic inflammation of the joints leads to joint destruction. To date, the best predictor of radiographic progression for patients with early RA is the presence of radiographic erosions at baseline, but a limited number of predictive biomarkers of structural progression are currently used in daily practice. Here, we investigated Dickkopf-1 (DKK-1) and sclerostin (SOST) serum levels in patients with recent inflammatory arthritis from the ESPOIR cohort. This cohort is a prospective, multicenter French cohort of 813 patients with early arthritis. We observed that mean baseline DKK-1 level was higher among RA patients with than without radiological progression within the first 2 years of evolution. DKK-1 level was still associated with radiographic progression in a model including other main predictors of severity (erosions at baseline, and anti-CCP antibody positivity). This study demonstrates that increased DKK-1 level at baseline predicted structural progression after 2-year follow-up and suggests that DKK-1 might be a new structural biomarker for early RA.

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Figures

Figure 1
Figure 1. Increased expression of DKK-1 and decreased expression of SOST among patients with early rheumatoid arthritis (RA).
Sandwich ELISA or DKK-1 and SOST levels among patients with early RA from the ESPOIR cohort (n = 694) and age- and gender-matched controls (n = 60). (A) SOST level (p = 0.001) (parametric unpaired t-test). (B) DKK-1 level (p < 0.0001) (parametric unpaired t-test). Data are mean (bars) ± interquartile range (whiskers). Each dot represents one patient.
Figure 2
Figure 2. Correlations between serum DKK-1 level and RA activity factors.
(A) C-reactive protein (CRP) level. (B) Erythrocyte sedimentation rate (ESR). (C) Disease Activity in 28 joints.
Figure 3
Figure 3. Impact of CRP level on serum DKK-1 level.
DKK-1 level (pmol/L) in patients early RA patients with normal vs increased CRP level (threshold 6 mg/L; Ptrend = 0.06).
Figure 4
Figure 4. DKK-1 serum levels by typical erosive lesions at baseline.
DKK-1 level (pmol/L) in patients with normal X-rays (n = 590) and typical erosive lesions (n = 104) at baseline. Data are mean ± SD. (unpaired t test).
Figure 5
Figure 5. Risk of structural progression in early RA patients within the first 2 years of follow-up by quartiles (Q) of serum DKK-1 level.
DKK-1 serum levels among patients with early RA show a Gaussian distribution. Q1, <19.2; Q2, 19.2–27.3; Q3, 27.3–34.8, and Q4 >34.8 pmol/L.
See this image and copyright information in PMC

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