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

Gaetane Nocturne; Stephan Pavy; Saida Boudaoud; Raphaèle Seror; Philippe Goupille; Philippe Chanson; Désirée van der Heijde; Floris van Gaalen; Francis Berenbaum; Xavier Mariette; Karine Briot; Antoine Feydy; Pascal Claudepierre; Philippe Dieudé; Joanne Nithitham; Kimberly E Taylor; Lindsey A Criswell; Maxime Dougados; Christian Roux; Corinne Miceli-Richard

doi:10.1371/journal.pone.0134974

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

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

Authors

Gaetane Nocturne¹, Stephan Pavy², Saida Boudaoud¹, Raphaèle Seror², Philippe Goupille³, Philippe Chanson⁴, Désirée van der Heijde⁵, Floris van Gaalen⁶, Francis Berenbaum⁷, Xavier Mariette⁸, Karine Briot⁹, Antoine Feydy¹⁰, Pascal Claudepierre¹¹, Philippe Dieudé¹², Joanne Nithitham¹³, Kimberly E Taylor¹³, Lindsey A Criswell¹³, Maxime Dougados⁹, Christian Roux⁹, Corinne Miceli-Richard⁸

Affiliations

¹ Institut Pour la Santé et la Recherche Médicale (INSERM) U1184, Université Paris-Sud 11, Le kremlin Bicêtre, France.
² Service de rhumatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Le Kremlin Bicêtre, France.
³ Service de rhumatologie, CHU, Tours, France; UMR CNRS 7292, Université François Rabelais, Tours, France; CIC-INSERM 1415, Tours, France.
⁴ Service d'endocrinologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Le Kremlin Bicêtre, France.
⁵ Leiden University Medical Center, Leiden, The Netherlands.
⁶ Department of Rheumatology and Internal Medicine, LUMC, Leiden, The Netherlands.
⁷ Sorbonne Universités, UPMC University Paris 6, AP-HP, Hôpital Saint-Antoine, Rheumatology Department, Paris, France.
⁸ Institut Pour la Santé et la Recherche Médicale (INSERM) U1184, Université Paris-Sud 11, Le kremlin Bicêtre, France; Service de rhumatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Le Kremlin Bicêtre, France.
⁹ Service de Rhumatologie B, Assistance Publique-Hôpitaux de Paris (AP-HP); Université Paris-Descartes, Paris, France.
¹⁰ Service de radiologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
¹¹ Service de Rhumatologie, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (APHP), Créteil, France.
¹² Service de Rhumatologie, Hôpital Bichat, AP-HP, Paris, France.
¹³ Rosalind Russell / Ephraim P Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, San Francisco, United States of America.

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.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Adult
Back Pain / blood
Bone Morphogenetic Proteins / blood*
Cohort Studies
Cross-Sectional Studies
Female
France
Genetic Markers
Genotype
Humans
Intercellular Signaling Peptides and Proteins / blood*
Intercellular Signaling Peptides and Proteins / genetics
Male
Polymorphism, Single Nucleotide
Spondylarthritis / blood*
Wnt Signaling Pathway

Substances

Adaptor Proteins, Signal Transducing
Bone Morphogenetic Proteins
DKK1 protein, human
Genetic Markers
Intercellular Signaling Peptides and Proteins
SOST protein, human

Grants and funding

An unrestricted grant from Wyeth Pharmaceuticals was allocated for the first 5 years of the follow-up of the recruited patients. The DESIR-cohort is financially supported by unrestricted grants from both the French Society of Rheumatology, and 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. The Variété cohort was supported by a grant from the Programme Hospitalier de Recherche Clinique, French Ministry of Health (no. P081216 / IDRCB 2009-A00892-55). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.