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Multicenter Study
. 2015 Aug 27;10(8):e0134974.
doi: 10.1371/journal.pone.0134974. eCollection 2015.

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Gaetane Nocturne  1 , Stephan Pavy  2 , Saida Boudaoud  1 , Raphaèle Seror  2 , Philippe Goupille  3 , Philippe Chanson  4 , Désirée van der Heijde  5 , Floris van Gaalen  6 , Francis Berenbaum  7 , Xavier Mariette  8 , Karine Briot  9 , Antoine Feydy  10 , Pascal Claudepierre  11 , Philippe Dieudé  12 , Joanne Nithitham  13 , Kimberly E Taylor  13 , Lindsey A Criswell  13 , Maxime Dougados  9 , Christian Roux  9 , Corinne Miceli-Richard  8
Affiliations
Multicenter Study

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Gaetane Nocturne et al. PLoS One. .

Abstract

Objectives: To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.

Methods: The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls.

Results: Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10-9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels.

Conclusions: DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.

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Conflict of interest statement

Competing Interests: The authors have the following interests: This study was partly supported by an unrestricted grant from Wyeth Pharmaceuticals which was allocated for the first 5 years of the follow-up of the recruited patients. The DESIR-cohort is partly financially supported by an unrestricted grant from Pfizer Ltd, France. A research grant from Pfizer “Passerelle” was obtained for DKK-1 and SOST quantification for the entire cohort and for genetic analysis of the DKK-1 locus. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1
Fig 1. Serum sclerotin (SOST) level among patients with axial spondyloarthritis (SpA) and controls at baseline.
Each point represents 1 patient. Data are mean ± SD. ***p<0.0001.
Fig 2
Fig 2. Correlation of SOST serum level with age.
(A) (rs = 0.36; p<0.0001), C-reactive protein (CRP) level (B) (rs = -0.18; p = 0.0001), high-sensitivity CRP (hs-CRP) level (C) (rs = -0.22; p<0.0001), erythrocyte sedimentation rate (ESR) (D) (rs = -0.12, p = 0.007) and Dickkopf-1 (DKK-1) serum levels (E) (rs = 0.15, p = 0.0008); rs: Spearman correlation coefficient.
Fig 3
Fig 3
(A) Serum DKK-1 level among axial SpA patients and controls at baseline. Each point represents 1 patient. Data are mean ± SD. *** p< 0.0001. (B) Distribution of DKK-1 levels in controls and axial SpA patients.
Fig 4
Fig 4. Correlation of DKK-1 serum level with systemic inflammation assessed by ESR.
(A) (rs = 0.1, p = 0.03), CRP level (B) (rs = 0.17; p = 0.0001), hs-CRP level (C) (rs = 0.14; p = 0.003), Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR (D) (rs = 0.11; p = 0.02) and ASDAS-CRP level (E) (rs = 0.13; p = 0.004); rs: Spearman correlation coefficient.
See this image and copyright information in PMC

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